Skip to main content

Advertisement

SpringerLink
Log in

Monocyte chemoattractant protein-1 and the blood–brain barrier

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

The blood–brain barrier (BBB) is a dynamic structure that maintains the homeostasis of the brain and thus proper neurological functions. BBB compromise has been found in many pathological conditions, including neuroinflammation. Monocyte chemoattractant protein-1 (MCP1), a chemokine that is transiently and significantly up-regulated during inflammation, is able to disrupt the integrity of BBB and modulate the progression of various diseases, including excitotoxic injury and hemorrhage. In this review, we first introduce the biochemistry and biology of MCP1, and then summarize the effects of MCP1 on BBB integrity as well as individual BBB components.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Glabinski AR, Balasingam V, Tani M, Kunkel SL, Strieter RM, Yong VW, Ransohoff RM (1996) Chemokine monocyte chemoattractant protein-1 is expressed by astrocytes after mechanical injury to the brain. J Immunol 156:4363–4368

    CAS  PubMed  Google Scholar 

  2. Hulkower K, Brosnan CF, Aquino DA, Cammer W, Kulshrestha S, Guida MP, Rapoport DA, Berman JW (1993) Expression of CSF-1, c-fms, and MCP-1 in the central nervous system of rats with experimental allergic encephalomyelitis. J Immunol 150:2525–2533

    CAS  PubMed  Google Scholar 

  3. Lahrtz F, Piali L, Spanaus KS, Seebach J, Fontana A (1998) Chemokines and chemotaxis of leukocytes in infectious meningitis. J Neuroimmunol 85:33–43

    CAS  PubMed  Google Scholar 

  4. Miller RJ, Meucci O (1999) AIDS and the brain: is there a chemokine connection? Trends Neurosci 22:471–479

    CAS  PubMed  Google Scholar 

  5. Wu VY, Walz DA, McCoy LE (1977) Purification and characterization of human and bovine platelet factor 4. Prep Biochem 7:479–493

    CAS  PubMed  Google Scholar 

  6. Ruiter DJ, Schlingemann RO, Westphal JR, Denijn M, Rietveld FJ, De Waal RM (1993). Angiogenesis in wound healing and tumor metastasis. Behring Inst Mitt 258–272

  7. Murphy PM (1994) The molecular biology of leukocyte chemoattractant receptors. Annu Rev Immunol 12:593–633

    CAS  PubMed  Google Scholar 

  8. Rollins BJ (1997) Chemokines. Blood 90:909–928

    CAS  PubMed  Google Scholar 

  9. Yoshimura T, Yuhki N, Moore SK, Appella E, Lerman MI, Leonard EJ (1989) Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE. FEBS Lett 244:487–493

    CAS  PubMed  Google Scholar 

  10. Campbell JJ, Butcher EC (2000) Chemokines in tissue-specific and microenvironment-specific lymphocyte homing. Curr Opin Immunol 12:336–341

    CAS  PubMed  Google Scholar 

  11. Cardona AE, Li M, Liu L, Savarin C, Ransohoff RM (2008) Chemokines in and out of the central nervous system: much more than chemotaxis and inflammation. J Leukoc Biol 84:587–594

    CAS  PubMed  Google Scholar 

  12. Tran PB, Miller RJ (2003) Chemokine receptors: signposts to brain development and disease. Nat Rev Neurosci 4:444–455

    CAS  PubMed  Google Scholar 

  13. Ransohoff RM (2002) The chemokine system in neuroinflammation: an update. J Infect Dis 186(Suppl 2):S152–S156

    CAS  PubMed  Google Scholar 

  14. Andjelkovic AV, Kerkovich D, Shanley J, Pulliam L, Pachter JS (1999) Expression of binding sites for beta chemokines on human astrocytes. Glia 28:225–235

    CAS  PubMed  Google Scholar 

  15. Andjelkovic AV, Pachter JS (2000) Characterization of binding sites for chemokines MCP-1 and MIP-1alpha on human brain microvessels. J Neurochem 75:1898–1906

    CAS  PubMed  Google Scholar 

  16. Andjelkovic AV, Spencer DD, Pachter JS (1999) Visualization of chemokine binding sites on human brain microvessels. J Cell Biol 145:403–412

    CAS  PubMed  Google Scholar 

  17. Boddeke EW, Meigel I, Frentzel S, Gourmala NG, Harrison JK, Buttini M, Spleiss O, Gebicke-Harter P (1999) Cultured rat microglia express functional beta-chemokine receptors. J Neuroimmunol 98:176–184

    CAS  PubMed  Google Scholar 

  18. Dicou E, Vincent JP, Mazella J (2004) Neurotensin receptor-3/sortilin mediates neurotensin-induced cytokine/chemokine expression in a murine microglial cell line. J Neurosci Res 78:92–99

    CAS  PubMed  Google Scholar 

  19. Horuk R, Martin AW, Wang Z, Schweitzer L, Gerassimides A, Guo H, Lu Z, Hesselgesser J, Perez HD, Kim J et al (1997) Expression of chemokine receptors by subsets of neurons in the central nervous system. J Immunol 158:2882–2890

    CAS  PubMed  Google Scholar 

  20. Kalehua AN, Nagel JE, Whelchel LM, Gides JJ, Pyle RS, Smith RJ, Kusiak JW, Taub DD (2004) Monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 are involved in both excitotoxin-induced neurodegeneration and regeneration. Exp Cell Res 297:197–211

    CAS  PubMed  Google Scholar 

  21. Mahad DJ, Ransohoff RM (2003) The role of MCP-1 (CCL2) and CCR2 in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Semin Immunol 15:23–32

    CAS  PubMed  Google Scholar 

  22. Mahajan SD, Schwartz SA, Aalinkeel R, Chawda RP, Sykes DE, Nair MP (2005) Morphine modulates chemokine gene regulation in normal human astrocytes. Clin Immunol 115:323–332

    CAS  PubMed  Google Scholar 

  23. Meeuwsen S, Bsibsi M, Persoon-Deen C, Ravid R, van Noort JM (2005) Cultured human adult microglia from different donors display stable cytokine, chemokine and growth factor gene profiles but respond differently to a pro-inflammatory stimulus. NeuroImmunoModulation 12:235–245

    CAS  PubMed  Google Scholar 

  24. Mennicken F, Maki R, de Souza EB, Quirion R (1999) Chemokines and chemokine receptors in the CNS: a possible role in neuroinflammation and patterning. Trends Pharmacol Sci 20:73–78

    CAS  PubMed  Google Scholar 

  25. Storer PD, Xu J, Chavis J, Drew PD (2005) Peroxisome proliferator-activated receptor-gamma agonists inhibit the activation of microglia and astrocytes: implications for multiple sclerosis. J Neuroimmunol 161:113–122

    CAS  PubMed  Google Scholar 

  26. Wittendorp MC, Boddeke HW, Biber K (2004) Adenosine A3 receptor-induced CCL2 synthesis in cultured mouse astrocytes. Glia 46:410–418

    PubMed  Google Scholar 

  27. Zeng HY, Zhu XA, Zhang C, Yang LP, Wu LM, Tso MO (2005) Identification of sequential events and factors associated with microglial activation, migration, and cytotoxicity in retinal degeneration in rd mice. Invest Ophthalmol Vis Sci 46:2992–2999

    PubMed  Google Scholar 

  28. Hoogewerf AJ, Kuschert GS, Proudfoot AE, Borlat F, Clark-Lewis I, Power CA, Wells TN (1997) Glycosaminoglycans mediate cell surface oligomerization of chemokines. Biochemistry 36:13570–13578

    CAS  PubMed  Google Scholar 

  29. Kuschert GS, Coulin F, Power CA, Proudfoot AE, Hubbard RE, Hoogewerf AJ, Wells TN (1999) Glycosaminoglycans interact selectively with chemokines and modulate receptor binding and cellular responses. Biochemistry 38:12959–12968

    CAS  PubMed  Google Scholar 

  30. Middleton J, Neil S, Wintle J, Clark-Lewis I, Moore H, Lam C, Auer M, Hub E, Rot A (1997) Transcytosis and surface presentation of IL-8 by venular endothelial cells. Cell 91:385–395

    CAS  PubMed  Google Scholar 

  31. Middleton J, Patterson AM, Gardner L, Schmutz C, Ashton BA (2002) Leukocyte extravasation: chemokine transport and presentation by the endothelium. Blood 100:3853–3860

    CAS  PubMed  Google Scholar 

  32. Rot A (1992) Endothelial cell binding of NAP-1/IL-8: role in neutrophil emigration. Immunol Today 13:291–294

    CAS  PubMed  Google Scholar 

  33. Rot A (1993) Neutrophil attractant/activation protein-1 (interleukin-8) induces in vitro neutrophil migration by haptotactic mechanism. Eur J Immunol 23:303–306

    CAS  PubMed  Google Scholar 

  34. Wagner L, Yang OO, Garcia-Zepeda EA, Ge Y, Kalams SA, Walker BD, Pasternack MS, Luster AD (1998) Beta-chemokines are released from HIV-1-specific cytolytic T-cell granules complexed to proteoglycans. Nature 391:908–911

    CAS  PubMed  Google Scholar 

  35. Lau EK, Paavola CD, Johnson Z, Gaudry JP, Geretti E, Borlat F, Kungl AJ, Proudfoot AE, Handel TM (2004) Identification of the glycosaminoglycan binding site of the CC chemokine, MCP-1: implications for structure and function in vivo. J Biol Chem 279:22294–22305

    CAS  PubMed  Google Scholar 

  36. Wang L, Fuster M, Sriramarao P, Esko JD (2005) Endothelial heparan sulfate deficiency impairs L-selectin- and chemokine-mediated neutrophil trafficking during inflammatory responses. Nat Immunol 6:902–910

    CAS  PubMed  Google Scholar 

  37. Ernst CA, Zhang YJ, Hancock PR, Rutledge BJ, Corless CL, Rollins BJ (1994) Biochemical and biologic characterization of murine monocyte chemoattractant protein-1. Identification of two functional domains. J Immunol 152:3541–3549

    CAS  PubMed  Google Scholar 

  38. Yao Y, Tsirka SE (2010) The C terminus of mouse monocyte chemoattractant protein 1 (MCP1) mediates MCP1 dimerization while blocking its chemotactic potency. J Biol Chem 285:31509–31516

    CAS  PubMed  Google Scholar 

  39. Zhang Y, Rollins BJ (1995) A dominant negative inhibitor indicates that monocyte chemoattractant protein 1 functions as a dimer. Mol Cell Biol 15:4851–4855

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Paavola CD, Hemmerich S, Grunberger D, Polsky I, Bloom A, Freedman R, Mulkins M, Bhakta S, McCarley D, Wiesent L et al (1998) Monomeric monocyte chemoattractant protein-1 (MCP-1) binds and activates the MCP-1 receptor CCR2B. J Biol Chem 273:33157–33165

    CAS  PubMed  Google Scholar 

  41. Banisadr G, Queraud-Lesaux F, Boutterin MC, Pelaprat D, Zalc B, Rostene W, Haour F, Parsadaniantz SM (2002) Distribution, cellular localization and functional role of CCR2 chemokine receptors in adult rat brain. J Neurochem 81:257–269

    CAS  PubMed  Google Scholar 

  42. Ge S, Song L, Serwanski DR, Kuziel WA, Pachter JS (2008) Transcellular transport of CCL2 across brain microvascular endothelial cells. J Neurochem 104:1219–1232

    CAS  PubMed  Google Scholar 

  43. Gong JH, Ratkay LG, Waterfield JD, Clark-Lewis I (1997) An antagonist of monocyte chemoattractant protein 1 (MCP-1) inhibits arthritis in the MRL-lpr mouse model. J Exp Med 186:131–137

    CAS  PubMed Central  PubMed  Google Scholar 

  44. Gouwy M, Struyf S, Catusse J, Proost P, Van Damme J (2004) Synergy between proinflammatory ligands of G protein-coupled receptors in neutrophil activation and migration. J Leukoc Biol 76:185–194

    CAS  PubMed  Google Scholar 

  45. Wain JH, Kirby JA, Ali S (2002) Leucocyte chemotaxis: examination of mitogen-activated protein kinase and phosphoinositide 3-kinase activation by Monocyte Chemoattractant Proteins-1, -2, -3 and -4. Clin Exp Immunol 127:436–444

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Charo IF, Myers SJ, Herman A, Franci C, Connolly AJ, Coughlin SR (1994) Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails. Proc Natl Acad Sci USA 91:2752–2756

    CAS  PubMed  Google Scholar 

  47. Bartoli C, Civatte M, Pellissier JF, Figarella-Branger D (2001) CCR2A and CCR2B, the two isoforms of the monocyte chemoattractant protein-1 receptor are up-regulated and expressed by different cell subsets in idiopathic inflammatory myopathies. Acta Neuropathol 102:385–392

    CAS  PubMed  Google Scholar 

  48. Guillemin GJ, Brew BJ (2004) Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification. J Leukoc Biol 75:388–397

    CAS  PubMed  Google Scholar 

  49. Engelhardt B, Ransohoff RM (2012) Capture, crawl, cross: the T cell code to breach the blood-brain barriers. Trends Immunol 33:579–589

    CAS  PubMed  Google Scholar 

  50. Barzo P, Marmarou A, Fatouros P, Hayasaki K, Corwin F (1997) Contribution of vasogenic and cellular edema to traumatic brain swelling measured by diffusion-weighted imaging. J Neurosurg 87:900–907

    CAS  PubMed  Google Scholar 

  51. Sixt M, Engelhardt B, Pausch F, Hallmann R, Wendler O, Sorokin LM (2001) Endothelial cell laminin isoforms, laminins 8 and 10, play decisive roles in T cell recruitment across the blood-brain barrier in experimental autoimmune encephalomyelitis. J Cell Biol 153:933–946

    CAS  PubMed  Google Scholar 

  52. Janzer RC, Raff MC (1987) Astrocytes induce blood-brain barrier properties in endothelial cells. Nature 325:253–257

    CAS  PubMed  Google Scholar 

  53. Papadopoulos MC, Saadoun S, Woodrow CJ, Davies DC, Costa-Martins P, Moss RF, Krishna S, Bell BA (2001) Occludin expression in microvessels of neoplastic and non-neoplastic human brain. Neuropathol Appl Neurobiol 27:384–395

    CAS  PubMed  Google Scholar 

  54. Belayev L, Busto R, Zhao W, Ginsberg MD (1996) Quantitative evaluation of blood-brain barrier permeability following middle cerebral artery occlusion in rats. Brain Res 739:88–96

    CAS  PubMed  Google Scholar 

  55. Benchenane K, Lopez-Atalaya JP, Fernandez-Monreal M, Touzani O, Vivien D (2004) Equivocal roles of tissue-type plasminogen activator in stroke-induced injury. Trends Neurosci 27:155–160

    CAS  PubMed  Google Scholar 

  56. Moskowitz MA, Lo EH, Iadecola C (2010) The science of stroke: mechanisms in search of treatments. Neuron 67:181–198

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Bell RD, Winkler EA, Sagare AP, Singh I, LaRue B, Deane R, Zlokovic BV (2010) Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron 68:409–427

    CAS  PubMed Central  PubMed  Google Scholar 

  58. Iadecola C (2010) The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia. Acta Neuropathol 120:287–296

    PubMed Central  PubMed  Google Scholar 

  59. Kortekaas R, Leenders KL, van Oostrom JC, Vaalburg W, Bart J, Willemsen AT, Hendrikse NH (2005) Blood-brain barrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol 57:176–179

    CAS  PubMed  Google Scholar 

  60. Selkoe DJ (2004) Alzheimer disease: mechanistic understanding predicts novel therapies. Ann Intern Med 140:627–638

    CAS  PubMed  Google Scholar 

  61. Zlokovic BV (2005) Neurovascular mechanisms of Alzheimer’s neurodegeneration. Trends Neurosci 28:202–208

    CAS  PubMed  Google Scholar 

  62. Garbuzova-Davis S, Rodrigues MC, Hernandez-Ontiveros DG, Louis MK, Willing AE, Borlongan CV, Sanberg PR (2011) Amyotrophic lateral sclerosis: a neurovascular disease. Brain Res 1398:113–125

    CAS  PubMed  Google Scholar 

  63. Blamire AM, Anthony DC, Rajagopalan B, Sibson NR, Perry VH, Styles P (2000) Interleukin-1beta -induced changes in blood-brain barrier permeability, apparent diffusion coefficient, and cerebral blood volume in the rat brain: a magnetic resonance study. J Neurosci 20:8153–8159

    CAS  PubMed  Google Scholar 

  64. Oshima T, Laroux FS, Coe LL, Morise Z, Kawachi S, Bauer P, Grisham MB, Specian RD, Carter P, Jennings S et al (2001) Interferon-gamma and interleukin-10 reciprocally regulate endothelial junction integrity and barrier function. Microvasc Res 61:130–143

    CAS  PubMed  Google Scholar 

  65. Stamatovic SM, Dimitrijevic OB, Keep RF, Andjelkovic AV (2006) Protein kinase Calpha-RhoA cross-talk in CCL2-induced alterations in brain endothelial permeability. J Biol Chem 281:8379–8388

    CAS  PubMed  Google Scholar 

  66. Stamatovic SM, Keep RF, Kunkel SL, Andjelkovic AV (2003) Potential role of MCP-1 in endothelial cell tight junction ‘opening’: signaling via Rho and Rho kinase. J Cell Sci 116:4615–4628

    CAS  PubMed  Google Scholar 

  67. Stamatovic SM, Shakui P, Keep RF, Moore BB, Kunkel SL, Van Rooijen N, Andjelkovic AV (2005) Monocyte chemoattractant protein-1 regulation of blood-brain barrier permeability. J Cereb Blood Flow Metab 25:593–606

    CAS  PubMed  Google Scholar 

  68. Wolburg H, Lippoldt A (2002) Tight junctions of the blood-brain barrier: development, composition and regulation. Vascul Pharmacol 38:323–337

    CAS  PubMed  Google Scholar 

  69. Yang GY, Gong C, Qin Z, Liu XH, Lorris Betz A (1999) Tumor necrosis factor alpha expression produces increased blood-brain barrier permeability following temporary focal cerebral ischemia in mice. Brain Res Mol Brain Res 69:135–143

    CAS  PubMed  Google Scholar 

  70. Yao Y, Tsirka SE (2011) Mouse MCP1 C-terminus inhibits human MCP1-induced chemotaxis and BBB compromise. J Neurochem 118:215–223

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Yao Y, Tsirka SE (2011) Truncation of monocyte chemoattractant protein 1 by plasmin promotes blood-brain barrier disruption. J Cell Sci 124:1486–1495

    CAS  PubMed  Google Scholar 

  72. Dimitrijevic OB, Stamatovic SM, Keep RF, Andjelkovic AV (2006) Effects of the chemokine CCL2 on blood-brain barrier permeability during ischemia-reperfusion injury. J Cereb Blood Flow Metab 26:797–810

    CAS  PubMed  Google Scholar 

  73. Reijerkerk A, Kooij G, van der Pol SM, Leyen T, van Het Hof B, Couraud PO, Vivien D, Dijkstra CD, de Vries HE (2008) Tissue-type plasminogen activator is a regulator of monocyte diapedesis through the brain endothelial barrier. J Immunol 181:3567–3574

    CAS  PubMed  Google Scholar 

  74. Kataoka K, Asai T, Taneda M, Ueshima S, Matsuo O, Kuroda R, Kawabata A, Carmeliet P (2000) Roles of urokinase type plasminogen activator in a brain stab wound. Brain Res 887:187–190

    CAS  PubMed  Google Scholar 

  75. Abbott NJ (2002) Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat 200:629–638

    CAS  PubMed  Google Scholar 

  76. Fenstermacher J, Gross P, Sposito N, Acuff V, Pettersen S, Gruber K (1988) Structural and functional variations in capillary systems within the brain. Ann NY Acad Sci 529:21–30

    CAS  PubMed  Google Scholar 

  77. Kniesel U, Wolburg H (2000) Tight junctions of the blood-brain barrier. Cell Mol Neurobiol 20:57–76

    CAS  PubMed  Google Scholar 

  78. Oldendorf WH, Cornford ME, Brown WJ (1977) The large apparent work capability of the blood-brain barrier: a study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Ann Neurol 1:409–417

    CAS  PubMed  Google Scholar 

  79. Sedlakova R, Shivers RR, Del Maestro RF (1999) Ultrastructure of the blood-brain barrier in the rabbit. J Submicrosc Cytol Pathol 31:149–161

    CAS  PubMed  Google Scholar 

  80. Schulze C, Firth JA (1993) Immunohistochemical localization of adherens junction components in blood-brain barrier microvessels of the rat. J Cell Sci 104(Pt 3):773–782

    PubMed  Google Scholar 

  81. Vorbrodt AW, Dobrogowska DH (2003) Molecular anatomy of intercellular junctions in brain endothelial and epithelial barriers: electron microscopist’s view. Brain Res Brain Res Rev 42:221–242

    CAS  PubMed  Google Scholar 

  82. Bazzoni G, Dejana E (2004) Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev 84:869–901

    CAS  PubMed  Google Scholar 

  83. Romero IA, Radewicz K, Jubin E, Michel CC, Greenwood J, Couraud PO, Adamson P (2003) Changes in cytoskeletal and tight junctional proteins correlate with decreased permeability induced by dexamethasone in cultured rat brain endothelial cells. Neurosci Lett 344:112–116

    CAS  PubMed  Google Scholar 

  84. Citi S, Cordenonsi M (1998) Tight junction proteins. Biochim Biophys Acta 1448:1–11

    CAS  PubMed  Google Scholar 

  85. Huber JD, Egleton RD, Davis TP (2001) Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier. Trends Neurosci 24:719–725

    CAS  PubMed  Google Scholar 

  86. Forster C (2008) Tight junctions and the modulation of barrier function in disease. Histochem Cell Biol 130:55–70

    PubMed Central  PubMed  Google Scholar 

  87. Michel CC, Curry FE (1999) Microvascular permeability. Physiol Rev 79:703–761

    CAS  PubMed  Google Scholar 

  88. Mitic LL, Anderson JM (1998) Molecular architecture of tight junctions. Annu Rev Physiol 60:121–142

    CAS  PubMed  Google Scholar 

  89. Ogunrinade O, Kameya GT, Truskey GA (2002) Effect of fluid shear stress on the permeability of the arterial endothelium. Ann Biomed Eng 30:430–446

    PubMed  Google Scholar 

  90. Bolton SJ, Anthony DC, Perry VH (1998) Loss of the tight junction proteins occludin and zonula occludens-1 from cerebral vascular endothelium during neutrophil-induced blood-brain barrier breakdown in vivo. Neuroscience 86:1245–1257

    CAS  PubMed  Google Scholar 

  91. Brown RC, Davis TP (2005) Hypoxia/aglycemia alters expression of occludin and actin in brain endothelial cells. Biochem Biophys Res Commun 327:1114–1123

    CAS  PubMed  Google Scholar 

  92. Huber JD, Hau VS, Borg L, Campos CR, Egleton RD, Davis TP (2002) Blood-brain barrier tight junctions are altered during a 72-h exposure to lambda-carrageenan-induced inflammatory pain. Am J Physiol Heart Circ Physiol 283:H1531–H1537

    CAS  PubMed  Google Scholar 

  93. McCarthy KM, Skare IB, Stankewich MC, Furuse M, Tsukita S, Rogers RA, Lynch RD, Schneeberger EE (1996) Occludin is a functional component of the tight junction. J Cell Sci 109(Pt 9):2287–2298

    CAS  PubMed  Google Scholar 

  94. Andreeva AY, Krause E, Muller EC, Blasig IE, Utepbergenov DI (2001) Protein kinase C regulates the phosphorylation and cellular localization of occludin. J Biol Chem 276:38480–38486

    CAS  PubMed  Google Scholar 

  95. Clarke H, Soler AP, Mullin JM (2000) Protein kinase C activation leads to dephosphorylation of occludin and tight junction permeability increase in LLC-PK1 epithelial cell sheets. J Cell Sci 113(Pt 18):3187–3196

    CAS  PubMed  Google Scholar 

  96. Hirase T, Kawashima S, Wong EY, Ueyama T, Rikitake Y, Tsukita S, Yokoyama M, Staddon JM (2001) Regulation of tight junction permeability and occludin phosphorylation by Rhoa-p160ROCK-dependent and -independent mechanisms. J Biol Chem 276:10423–10431

    CAS  PubMed  Google Scholar 

  97. Kale G, Naren AP, Sheth P, Rao RK (2003) Tyrosine phosphorylation of occludin attenuates its interactions with ZO-1, ZO-2, and ZO-3. Biochem Biophys Res Commun 302:324–329

    CAS  PubMed  Google Scholar 

  98. Rao RK, Basuroy S, Rao VU, Karnaky KJ Jr, Gupta A (2002) Tyrosine phosphorylation and dissociation of occludin-ZO-1 and E-cadherin-beta-catenin complexes from the cytoskeleton by oxidative stress. Biochem J 368:471–481

    CAS  PubMed  Google Scholar 

  99. Sakakibara A, Furuse M, Saitou M, Ando-Akatsuka Y, Tsukita S (1997) Possible involvement of phosphorylation of occludin in tight junction formation. J Cell Biol 137:1393–1401

    CAS  PubMed  Google Scholar 

  100. Wachtel M, Frei K, Ehler E, Fontana A, Winterhalter K, Gloor SM (1999) Occludin proteolysis and increased permeability in endothelial cells through tyrosine phosphatase inhibition. J Cell Sci 112(Pt 23):4347–4356

    CAS  PubMed  Google Scholar 

  101. Stevenson BR, Siliciano JD, Mooseker MS, Goodenough DA (1986) Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia. J Cell Biol 103:755–766

    CAS  PubMed  Google Scholar 

  102. Fanning AS, Jameson BJ, Jesaitis LA, Anderson JM (1998) The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J Biol Chem 273:29745–29753

    CAS  PubMed  Google Scholar 

  103. Abbruscato TJ, Lopez SP, Mark KS, Hawkins BT, Davis TP (2002) Nicotine and cotinine modulate cerebral microvascular permeability and protein expression of ZO-1 through nicotinic acetylcholine receptors expressed on brain endothelial cells. J Pharm Sci 91:2525–2538

    CAS  PubMed  Google Scholar 

  104. Fischer S, Wobben M, Marti HH, Renz D, Schaper W (2002) Hypoxia-induced hyperpermeability in brain microvessel endothelial cells involves VEGF-mediated changes in the expression of zonula occludens-1. Microvasc Res 63:70–80

    CAS  PubMed  Google Scholar 

  105. Mark KS, Davis TP (2002) Cerebral microvascular changes in permeability and tight junctions induced by hypoxia-reoxygenation. Am J Physiol Heart Circ Physiol 282:H1485–H1494

    CAS  PubMed  Google Scholar 

  106. Balda MS, Matter K (2000) The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression. EMBO J 19:2024–2033

    CAS  PubMed  Google Scholar 

  107. Gottardi CJ, Arpin M, Fanning AS, Louvard D (1996) The junction-associated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell–cell contacts. Proc Natl Acad Sci USA 93:10779–10784

    CAS  PubMed  Google Scholar 

  108. Hawkins BT, Abbruscato TJ, Egleton RD, Brown RC, Huber JD, Campos CR, Davis TP (2004) Nicotine increases in vivo blood-brain barrier permeability and alters cerebral microvascular tight junction protein distribution. Brain Res 1027:48–58

    CAS  PubMed  Google Scholar 

  109. Riesen FK, Rothen-Rutishauser B, Wunderli-Allenspach H (2002) A ZO1-GFP fusion protein to study the dynamics of tight junctions in living cells. Histochem Cell Biol 117:307–315

    CAS  PubMed  Google Scholar 

  110. Clarke H, Marano CW, Peralta Soler A, Mullin JM (2000) Modification of tight junction function by protein kinase C isoforms. Adv Drug Deliv Rev 41:283–301

    CAS  PubMed  Google Scholar 

  111. Farshori P, Kachar B (1999) Redistribution and phosphorylation of occludin during opening and resealing of tight junctions in cultured epithelial cells. J Membr Biol 170:147–156

    CAS  PubMed  Google Scholar 

  112. Ward PD, Klein RR, Troutman MD, Desai S, Thakker DR (2002) Phospholipase C-gamma modulates epithelial tight junction permeability through hyperphosphorylation of tight junction proteins. J Biol Chem 277:35760–35765

    CAS  PubMed  Google Scholar 

  113. Tsukamoto T, Nigam SK (1997) Tight junction proteins form large complexes and associate with the cytoskeleton in an ATP depletion model for reversible junction assembly. J Biol Chem 272:16133–16139

    CAS  PubMed  Google Scholar 

  114. Tsukamoto T, Nigam SK (1999) Role of tyrosine phosphorylation in the reassembly of occludin and other tight junction proteins. Am J Physiol 276:F737–F750

    CAS  PubMed  Google Scholar 

  115. Harhaj NS, Barber AJ, Antonetti DA (2002) Platelet-derived growth factor mediates tight junction redistribution and increases permeability in MDCK cells. J Cell Physiol 193:349–364

    CAS  PubMed  Google Scholar 

  116. Pedram A, Razandi M, Levin ER (2002) Deciphering vascular endothelial cell growth factor/vascular permeability factor signaling to vascular permeability. Inhibition by atrial natriuretic peptide. J Biol Chem 277:44385–44398

    CAS  PubMed  Google Scholar 

  117. Hicks K, O’Neil RG, Dubinsky WS, Brown RC (2010) TRPC-mediated actin-myosin contraction is critical for BBB disruption following hypoxic stress. Am J Physiol Cell Physiol 298:C1583–C1593

    CAS  PubMed  Google Scholar 

  118. Stephan CC, Brock TA (1996) Vascular endothelial growth factor, a multifunctional polypeptide. PR Health Sci J 15:169–178

    CAS  Google Scholar 

  119. van Nieuw Amerongen GP, van Delft S, Vermeer MA, Collard JG, van Hinsbergh VW (2000) Activation of RhoA by thrombin in endothelial hyperpermeability: role of Rho kinase and protein tyrosine kinases. Circ Res 87:335–340

    PubMed  Google Scholar 

  120. Bretscher A, Gary R, Berryman M (1995) Soluble ezrin purified from placenta exists as stable monomers and elongated dimers with masked C-terminal ezrin-radixin-moesin association domains. Biochemistry 34:16830–16837

    CAS  PubMed  Google Scholar 

  121. Louvet-Vallee S (2000) ERM proteins: from cellular architecture to cell signaling. Biol Cell 92:305–316

    CAS  PubMed  Google Scholar 

  122. Pearson MA, Reczek D, Bretscher A, Karplus PA (2000) Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain. Cell 101:259–270

    CAS  PubMed  Google Scholar 

  123. Stewart PA, Wiley MJ (1981) Developing nervous tissue induces formation of blood-brain barrier characteristics in invading endothelial cells: a study using quail–chick transplantation chimeras. Dev Biol 84:183–192

    CAS  PubMed  Google Scholar 

  124. Kacem K, Lacombe P, Seylaz J, Bonvento G (1998) Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: a confocal microscopy study. Glia 23:1–10

    CAS  PubMed  Google Scholar 

  125. Simard M, Arcuino G, Takano T, Liu QS, Nedergaard M (2003) Signaling at the gliovascular interface. J Neurosci 23:9254–9262

    CAS  PubMed  Google Scholar 

  126. Cohen-Kashi Malina K, Cooper I, Teichberg VI (2009) Closing the gap between the in vivo and in vitro blood-brain barrier tightness. Brain Res 1284:12–21

    CAS  PubMed  Google Scholar 

  127. Jain RK, di Tomaso E, Duda DG, Loeffler JS, Sorensen AG, Batchelor TT (2007) Angiogenesis in brain tumours. Nat Rev Neurosci 8:610–622

    CAS  PubMed  Google Scholar 

  128. Siddharthan V, Kim YV, Liu S, Kim KS (2007) Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells. Brain Res 1147:39–50

    CAS  PubMed Central  PubMed  Google Scholar 

  129. Tao-Cheng JH, Nagy Z, Brightman MW (1987) Tight junctions of brain endothelium in vitro are enhanced by astroglia. J Neurosci 7:3293–3299

    CAS  PubMed  Google Scholar 

  130. Willis CL, Nolan CC, Reith SN, Lister T, Prior MJ, Guerin CJ, Mavroudis G, Ray DE (2004) Focal astrocyte loss is followed by microvascular damage, with subsequent repair of the blood-brain barrier in the apparent absence of direct astrocytic contact. Glia 45:325–337

    PubMed  Google Scholar 

  131. Cardoso FL, Brites D, Brito MA (2010) Looking at the blood-brain barrier: molecular anatomy and possible investigation approaches. Brain Res Rev 64:328–363

    CAS  PubMed  Google Scholar 

  132. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD (2006) Blood-brain barrier: structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol 1:223–236

    PubMed  Google Scholar 

  133. Quaegebeur A, Lange C, Carmeliet P (2011) The neurovascular link in health and disease: molecular mechanisms and therapeutic implications. Neuron 71:406–424

    CAS  PubMed  Google Scholar 

  134. Lai CH, Kuo KH (2005) The critical component to establish in vitro BBB model: pericyte. Brain Res Brain Res Rev 50:258–265

    CAS  PubMed  Google Scholar 

  135. Wolburg H, Wolburg-Buchholz K, Fallier-Becker P, Noell S, Mack AF (2011) Structure and functions of aquaporin-4-based orthogonal arrays of particles. Int Rev Cell Mol Biol 287:1–41

    CAS  PubMed  Google Scholar 

  136. Daneman R, Zhou L, Kebede AA, Barres BA (2010) Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 468:562–566

    CAS  PubMed Central  PubMed  Google Scholar 

  137. Krum JM, Kenyon KL, Rosenstein JM (1997) Expression of blood-brain barrier characteristics following neuronal loss and astroglial damage after administration of anti-Thy-1 immunotoxin. Exp Neurol 146:33–45

    CAS  PubMed  Google Scholar 

  138. Menetski J, Mistry S, Lu M, Mudgett JS, Ransohoff RM, Demartino JA, Macintyre DE, Abbadie C (2007) Mice overexpressing chemokine ligand 2 (CCL2) in astrocytes display enhanced nociceptive responses. Neuroscience 149:706–714

    CAS  PubMed  Google Scholar 

  139. Huang D, Wujek J, Kidd G, He TT, Cardona A, Sasse ME, Stein EJ, Kish J, Tani M, Charo IF et al (2005) Chronic expression of monocyte chemoattractant protein-1 in the central nervous system causes delayed encephalopathy and impaired microglial function in mice. FASEB J 19:761–772

    CAS  PubMed  Google Scholar 

  140. Fouillet A, Mawson J, Suliman O, Sharrack B, Romero IA, Woodroofe MN (2012) CCL2 binding is CCR2 independent in primary adult human astrocytes. Brain Res 1437:115–126

    CAS  PubMed  Google Scholar 

  141. Quinones MP, Kalkonde Y, Estrada CA, Jimenez F, Ramirez R, Mahimainathan L, Mummidi S, Choudhury GG, Martinez H, Adams L et al (2008) Role of astrocytes and chemokine systems in acute TNFalpha induced demyelinating syndrome: CCR2-dependent signals promote astrocyte activation and survival via NF-kappaB and Akt. Mol Cell Neurosci 37:96–109

    CAS  PubMed Central  PubMed  Google Scholar 

  142. Ge S, Pachter JS (2004) Caveolin-1 knockdown by small interfering RNA suppresses responses to the chemokine monocyte chemoattractant protein-1 by human astrocytes. J Biol Chem 279:6688–6695

    CAS  PubMed  Google Scholar 

  143. Owens T, Bechmann I, Engelhardt B (2008) Perivascular spaces and the two steps to neuroinflammation. J Neuropathol Exp Neurol 67:1113–1121

    PubMed  Google Scholar 

  144. Agrawal S, Anderson P, Durbeej M, van Rooijen N, Ivars F, Opdenakker G, Sorokin LM (2006) Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation in experimental autoimmune encephalomyelitis. J Exp Med 203:1007–1019

    CAS  PubMed Central  PubMed  Google Scholar 

  145. Baumann E, Preston E, Slinn J, Stanimirovic D (2009) Post-ischemic hypothermia attenuates loss of the vascular basement membrane proteins, agrin and SPARC, and the blood-brain barrier disruption after global cerebral ischemia. Brain Res 1269:185–197

    CAS  PubMed  Google Scholar 

  146. Fukuda S, Fini CA, Mabuchi T, Koziol JA, Eggleston LL Jr, del Zoppo GJ (2004) Focal cerebral ischemia induces active proteases that degrade microvascular matrix. Stroke 35:998–1004

    CAS  PubMed Central  PubMed  Google Scholar 

  147. Yurchenco PD, Amenta PS, Patton BL (2004) Basement membrane assembly, stability and activities observed through a developmental lens. Matrix Biol 22:521–538

    CAS  PubMed  Google Scholar 

  148. Yurchenco PD, Patton BL (2009) Developmental and pathogenic mechanisms of basement membrane assembly. Curr Pharm Des 15:1277–1294

    CAS  PubMed Central  PubMed  Google Scholar 

  149. van Horssen J, Bo L, Vos CM, Virtanen I, de Vries HE (2005) Basement membrane proteins in multiple sclerosis-associated inflammatory cuffs: potential role in influx and transport of leukocytes. J Neuropathol Exp Neurol 64:722–729

    PubMed  Google Scholar 

  150. Barber AJ, Lieth E (1997) Agrin accumulates in the brain microvascular basal lamina during development of the blood-brain barrier. Dev Dyn 208:62–74

    CAS  PubMed  Google Scholar 

  151. del Zoppo GJ (2009) Relationship of neurovascular elements to neuron injury during ischemia. Cerebrovasc Dis 27(Suppl 1):65–76

    PubMed  Google Scholar 

  152. Del Zoppo GJ, Milner R, Mabuchi T, Hung S, Wang X, Koziol JA (2006) Vascular matrix adhesion and the blood-brain barrier. Biochem Soc Trans 34:1261–1266

    PubMed  Google Scholar 

  153. Kwon I, Kim EH, del Zoppo GJ, Heo JH (2009) Ultrastructural and temporal changes of the microvascular basement membrane and astrocyte interface following focal cerebral ischemia. J Neurosci Res 87:668–676

    CAS  PubMed Central  PubMed  Google Scholar 

  154. Lo EH, Rosenberg GA (2009) The neurovascular unit in health and disease: introduction. Stroke 40:S2–S3

    PubMed Central  PubMed  Google Scholar 

  155. Wang CX, Shuaib A (2007) Critical role of microvasculature basal lamina in ischemic brain injury. Prog Neurobiol 83:140–148

    CAS  PubMed  Google Scholar 

  156. Zhang X, Winkles JA, Gongora MC, Polavarapu R, Michaelson JS, Hahm K, Burkly L, Friedman M, Li XJ, Yepes M (2007) TWEAK-Fn14 pathway inhibition protects the integrity of the neurovascular unit during cerebral ischemia. J Cereb Blood Flow Metab 27:534–544

    PubMed  Google Scholar 

  157. Tilling T, Engelbertz C, Decker S, Korte D, Huwel S, Galla HJ (2002) Expression and adhesive properties of basement membrane proteins in cerebral capillary endothelial cell cultures. Cell Tissue Res 310:19–29

    CAS  PubMed  Google Scholar 

  158. Tilling T, Korte D, Hoheisel D, Galla HJ (1998) Basement membrane proteins influence brain capillary endothelial barrier function in vitro. J Neurochem 71:1151–1157

    CAS  PubMed  Google Scholar 

  159. Kim DS, Kang SI, Lee SY, Noh KT, Kim EC (2013). Involvement of SDF-1 and monocyte chemoattractant protein-1 in hydrogen peroxide-induced extracellular matrix degradation in human dental pulp cells. Int Endod J (in press)

  160. Park J, Ryu DR, Li JJ, Jung DS, Kwak SJ, Lee SH, Yoo TH, Han SH, Lee JE, Kim DK et al (2008) MCP-1/CCR2 system is involved in high glucose-induced fibronectin and type IV collagen expression in cultured mesangial cells. Am J Physiol Renal Physiol 295:F749–F757

    CAS  PubMed  Google Scholar 

  161. Arai M, Ikawa Y, Chujo S, Hamaguchi Y, Ishida W, Shirasaki F, Hasegawa M, Mukaida N, Fujimoto M, Takehara K (2013) Chemokine receptors CCR2 and CX3CR1 regulate skin fibrosis in the mouse model of cytokine-induced systemic sclerosis. J Dermatol Sci 69:250–258

    CAS  PubMed  Google Scholar 

  162. Lee SH, Kang HY, Kim KS, Nam BY, Paeng J, Kim S, Li JJ, Park JT, Kim DK, Han SH et al (2012) The monocyte chemoattractant protein-1 (MCP-1)/CCR2 system is involved in peritoneal dialysis-related epithelial-mesenchymal transition of peritoneal mesothelial cells. Lab Invest 92:1698–1711

    CAS  PubMed  Google Scholar 

  163. Greenlee KJ, Werb Z, Kheradmand F (2007) Matrix metalloproteinases in lung: multiple, multifarious, and multifaceted. Physiol Rev 87:69–98

    CAS  PubMed Central  PubMed  Google Scholar 

  164. Stamenkovic I (2003) Extracellular matrix remodelling: the role of matrix metalloproteinases. J Pathol 200:448–464

    CAS  PubMed  Google Scholar 

  165. Rouget C (1873) Mémoire sur le développement, la structure et les propriétés physiologiques des capillaires sanguins et lymphatiques. Archs Physiol Norm Pathol 5:603–663

    Google Scholar 

  166. Sa-Pereira I, Brites D, Brito MA (2012) Neurovascular unit: a focus on pericytes. Mol Neurobiol 45:327–347

    CAS  PubMed  Google Scholar 

  167. Armulik A, Genove G, Betsholtz C (2011) Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 21:193–215

    CAS  PubMed  Google Scholar 

  168. Dalkara T, Gursoy-Ozdemir Y, Yemisci M (2011) Brain microvascular pericytes in health and disease. Acta Neuropathol 122:1–9

    PubMed  Google Scholar 

  169. Dore-Duffy P (2008) Pericytes: pluripotent cells of the blood brain barrier. Curr Pharm Des 14:1581–1593

    CAS  PubMed  Google Scholar 

  170. Dore-Duffy P, Cleary K (2011) Morphology and properties of pericytes. Methods Mol Biol 686:49–68

    CAS  PubMed  Google Scholar 

  171. Engelhardt B, Sorokin L (2009) The blood-brain and the blood-cerebrospinal fluid barriers: function and dysfunction. Semin Immunopathol 31:497–511

    PubMed  Google Scholar 

  172. Frank RN, Dutta S, Mancini MA (1987) Pericyte coverage is greater in the retinal than in the cerebral capillaries of the rat. Invest Ophthalmol Vis Sci 28:1086–1091

    CAS  PubMed  Google Scholar 

  173. Fisher M (2009) Pericyte signaling in the neurovascular unit. Stroke 40:S13–S15

    CAS  PubMed Central  PubMed  Google Scholar 

  174. Krueger M, Bechmann I (2010) CNS pericytes: concepts, misconceptions, and a way out. Glia 58:1–10

    PubMed  Google Scholar 

  175. Nehls V, Drenckhahn D (1993) The versatility of microvascular pericytes: from mesenchyme to smooth muscle? Histochemistry 99:1–12

    CAS  PubMed  Google Scholar 

  176. Lindahl P, Johansson BR, Leveen P, Betsholtz C (1997) Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277:242–245

    CAS  PubMed  Google Scholar 

  177. Nehls V, Denzer K, Drenckhahn D (1992) Pericyte involvement in capillary sprouting during angiogenesis in situ. Cell Tissue Res 270:469–474

    CAS  PubMed  Google Scholar 

  178. Dermietzel R, Krause D (1991) Molecular anatomy of the blood-brain barrier as defined by immunocytochemistry. Int Rev Cytol 127:57–109

    CAS  PubMed  Google Scholar 

  179. Kunz J, Krause D, Kremer M, Dermietzel R (1994) The 140-kDa protein of blood-brain barrier-associated pericytes is identical to aminopeptidase N. J Neurochem 62:2375–2386

    CAS  PubMed  Google Scholar 

  180. Huang FJ, You WK, Bonaldo P, Seyfried TN, Pasquale EB, Stallcup WB (2010) Pericyte deficiencies lead to aberrant tumor vascularizaton in the brain of the NG2 null mouse. Dev Biol 344:1035–1046

    CAS  PubMed Central  PubMed  Google Scholar 

  181. Ozerdem U, Grako KA, Dahlin-Huppe K, Monosov E, Stallcup WB (2001) NG2 proteoglycan is expressed exclusively by mural cells during vascular morphogenesis. Dev Dyn 222:218–227

    CAS  PubMed  Google Scholar 

  182. Bondjers C, Kalen M, Hellstrom M, Scheidl SJ, Abramsson A, Renner O, Lindahl P, Cho H, Kehrl J, Betsholtz C (2003) Transcription profiling of platelet-derived growth factor-B-deficient mouse embryos identifies RGS5 as a novel marker for pericytes and vascular smooth muscle cells. Am J Pathol 162:721–729

    CAS  PubMed  Google Scholar 

  183. Cho H, Kozasa T, Bondjers C, Betsholtz C, Kehrl JH (2003) Pericyte-specific expression of Rgs5: implications for PDGF and EDG receptor signaling during vascular maturation. FASEB J 17:440–442

    CAS  PubMed  Google Scholar 

  184. Bandopadhyay R, Orte C, Lawrenson JG, Reid AR, De Silva S, Allt G (2001) Contractile proteins in pericytes at the blood-brain and blood-retinal barriers. J Neurocytol 30:35–44

    CAS  PubMed  Google Scholar 

  185. Nehls V, Drenckhahn D (1991) Heterogeneity of microvascular pericytes for smooth muscle type alpha-actin. J Cell Biol 113:147–154

    CAS  PubMed  Google Scholar 

  186. Thanabalasundaram G, Schneidewind J, Pieper C, Galla HJ (2011) The impact of pericytes on the blood-brain barrier integrity depends critically on the pericyte differentiation stage. Int J Biochem Cell Biol 43:1284–1293

    CAS  PubMed  Google Scholar 

  187. Etchevers HC, Vincent C, Le Douarin NM, Couly GF (2001) The cephalic neural crest provides pericytes and smooth muscle cells to all blood vessels of the face and forebrain. Development 128:1059–1068

    CAS  PubMed  Google Scholar 

  188. Heglind M, Cederberg A, Aquino J, Lucas G, Ernfors P, Enerback S (2005) Lack of the central nervous system- and neural crest-expressed forkhead gene Foxs1 affects motor function and body weight. Mol Cell Biol 25:5616–5625

    CAS  PubMed Central  PubMed  Google Scholar 

  189. Korn J, Christ B, Kurz H (2002) Neuroectodermal origin of brain pericytes and vascular smooth muscle cells. J Comp Neurol 442:78–88

    PubMed  Google Scholar 

  190. Que J, Wilm B, Hasegawa H, Wang F, Bader D, Hogan BL (2008) Mesothelium contributes to vascular smooth muscle and mesenchyme during lung development. Proc Natl Acad Sci USA 105:16626–16630

    CAS  PubMed  Google Scholar 

  191. Asahina K, Zhou B, Pu WT, Tsukamoto H (2011) Septum transversum-derived mesothelium gives rise to hepatic stellate cells and perivascular mesenchymal cells in developing mouse liver. Hepatology 53:983–995

    CAS  PubMed Central  PubMed  Google Scholar 

  192. Wilm B, Ipenberg A, Hastie ND, Burch JB, Bader DM (2005) The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature. Development 132:5317–5328

    CAS  PubMed  Google Scholar 

  193. Hess DC, Abe T, Hill WD, Studdard AM, Carothers J, Masuya M, Fleming PA, Drake CJ, Ogawa M (2004) Hematopoietic origin of microglial and perivascular cells in brain. Exp Neurol 186:134–144

    CAS  PubMed  Google Scholar 

  194. Dore-Duffy P, Katychev A, Wang X, Van Buren E (2006) CNS microvascular pericytes exhibit multipotential stem cell activity. J Cereb Blood Flow Metab 26:613–624

    CAS  PubMed  Google Scholar 

  195. Dente CJ, Steffes CP, Speyer C, Tyburski JG (2001) Pericytes augment the capillary barrier in in vitro cocultures. J Surg Res 97:85–91

    CAS  PubMed  Google Scholar 

  196. Nakagawa S, Deli MA, Kawaguchi H, Shimizudani T, Shimono T, Kittel A, Tanaka K, Niwa M (2009) A new blood-brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes. Neurochem Int 54:253–263

    CAS  PubMed  Google Scholar 

  197. Dohgu S, Takata F, Yamauchi A, Nakagawa S, Egawa T, Naito M, Tsuruo T, Sawada Y, Niwa M, Kataoka Y (2005) Brain pericytes contribute to the induction and up-regulation of blood-brain barrier functions through transforming growth factor-beta production. Brain Res 1038:208–215

    CAS  PubMed  Google Scholar 

  198. Edelman DA, Jiang Y, Tyburski J, Wilson RF, Steffes C (2006) Pericytes and their role in microvasculature homeostasis. J Surg Res 135:305–311

    CAS  PubMed  Google Scholar 

  199. Peppiatt CM, Howarth C, Mobbs P, Attwell D (2006) Bidirectional control of CNS capillary diameter by pericytes. Nature 443:700–704

    CAS  PubMed Central  PubMed  Google Scholar 

  200. Armulik A, Genove G, Mae M, Nisancioglu MH, Wallgard E, Niaudet C, He L, Norlin J, Lindblom P, Strittmatter K et al (2010) Pericytes regulate the blood-brain barrier. Nature 468:557–561

    CAS  PubMed  Google Scholar 

  201. Dore-Duffy P, Owen C, Balabanov R, Murphy S, Beaumont T, Rafols JA (2000) Pericyte migration from the vascular wall in response to traumatic brain injury. Microvasc Res 60:55–69

    CAS  PubMed  Google Scholar 

  202. Gonul E, Duz B, Kahraman S, Kayali H, Kubar A, Timurkaynak E (2002) Early pericyte response to brain hypoxia in cats: an ultrastructural study. Microvasc Res 64:116–119

    PubMed  Google Scholar 

  203. Chen YT, Chang FC, Wu CF, Chou YH, Hsu HL, Chiang WC, Shen J, Chen YM, Wu KD, Tsai TJ et al (2011) Platelet-derived growth factor receptor signaling activates pericyte-myofibroblast transition in obstructive and post-ischemic kidney fibrosis. Kidney Int 80:1170–1181

    CAS  PubMed  Google Scholar 

  204. Sheehan JJ, Zhou C, Gravanis I, Rogove AD, Wu YP, Bogenhagen DF, Tsirka SE (2007) Proteolytic activation of monocyte chemoattractant protein-1 by plasmin underlies excitotoxic neurodegeneration in mice. J Neurosci 27:1738–1745

    CAS  PubMed  Google Scholar 

  205. Zhang SX, Wang JJ, Dashti A, Wilson K, Zou MH, Szweda L, Ma JX, Lyons TJ (2008) Pigment epithelium-derived factor mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized low-density lipoprotein. J Mol Endocrinol 41:135–143

    CAS  PubMed Central  PubMed  Google Scholar 

  206. Chan WY, Kohsaka S, Rezaie P (2007) The origin and cell lineage of microglia: new concepts. Brain Res Rev 53:344–354

    CAS  PubMed  Google Scholar 

  207. Hailer NP, Heppner FL, Haas D, Nitsch R (1997) Fluorescent dye prelabelled microglial cells migrate into organotypic hippocampal slice cultures and ramify. Eur J Neurosci 9:863–866

    CAS  PubMed  Google Scholar 

  208. Ling EA (1979) Transformation of monocytes into amoeboid microglia in the corpus callosum of postnatal rats, as shown by labelling monocytes by carbon particles. J Anat 128:847–858

    CAS  PubMed  Google Scholar 

  209. Ono K, Takii T, Onozaki K, Ikawa M, Okabe M, Sawada M (1999) Migration of exogenous immature hematopoietic cells into adult mouse brain parenchyma under GFP-expressing bone marrow chimera. Biochem Biophys Res Commun 262:610–614

    CAS  PubMed  Google Scholar 

  210. Wu YP, McMahon E, Kraine MR, Tisch R, Meyers A, Frelinger J, Matsushima GK, Suzuki K (2000) Distribution and characterization of GFP(+) donor hematogenous cells in Twitcher mice after bone marrow transplantation. Am J Pathol 156:1849–1854

    CAS  PubMed  Google Scholar 

  211. Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER et al (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841–845

    CAS  PubMed Central  PubMed  Google Scholar 

  212. Buza-Vidas N, Woll P, Hultquist A, Duarte S, Lutteropp M, Bouriez-Jones T, Ferry H, Luc S, Jacobsen SE (2011) FLT3 expression initiates in fully multipotent mouse hematopoietic progenitor cells. Blood 118:1544–1548

    CAS  PubMed  Google Scholar 

  213. Erblich B, Zhu L, Etgen AM, Dobrenis K, Pollard JW (2011) Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits. PLoS ONE 6:e26317

    CAS  PubMed Central  PubMed  Google Scholar 

  214. Gomez Perdiguero E, Schulz C, Geissmann F (2013) Development and homeostasis of “resident” myeloid cells: the case of the microglia. Glia 61:112–120

    PubMed  Google Scholar 

  215. Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, Kaiser EA, Snyder LA, Pollard JW (2011) CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475:222–225

    CAS  PubMed Central  PubMed  Google Scholar 

  216. Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, Prinz M, Wu B, Jacobsen SE, Pollard JW et al (2012) A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336:86–90

    CAS  PubMed  Google Scholar 

  217. Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318

    CAS  PubMed  Google Scholar 

  218. Abromson-Leeman S, Hayashi M, Martin C, Sobel R, al-Sabbagh A, Weiner H, Dorf ME (1993) T cell responses to myelin basic protein in experimental autoimmune encephalomyelitis-resistant BALB/c mice. J Neuroimmunol 45:89–101

    CAS  PubMed  Google Scholar 

  219. Aloisi F (2001) Immune function of microglia. Glia 36:165–179

    CAS  PubMed  Google Scholar 

  220. Giulian D, Baker TJ (1986) Characterization of ameboid microglia isolated from developing mammalian brain. J Neurosci 6:2163–2178

    CAS  PubMed  Google Scholar 

  221. Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387–1394

    CAS  PubMed  Google Scholar 

  222. Kim SU, de Vellis J (2005) Microglia in health and disease. J Neurosci Res 81:302–313

    CAS  PubMed  Google Scholar 

  223. Nakajima K, Kohsaka S (2004) Microglia: neuroprotective and neurotrophic cells in the central nervous system. Curr Drug Targets Cardiovasc Haematol Disord 4:65–84

    CAS  PubMed  Google Scholar 

  224. Suzumura A, Mezitis SG, Gonatas NK, Silberberg DH (1987) MHC antigen expression on bulk isolated macrophage-microglia from newborn mouse brain: induction of Ia antigen expression by gamma-interferon. J Neuroimmunol 15:263–278

    CAS  PubMed  Google Scholar 

  225. Ulvestad E, Williams K, Bjerkvig R, Tiekotter K, Antel J, Matre R (1994) Human microglial cells have phenotypic and functional characteristics in common with both macrophages and dendritic antigen-presenting cells. J Leukoc Biol 56:732–740

    CAS  PubMed  Google Scholar 

  226. Elkabes S, DiCicco-Bloom EM, Black IB (1996) Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. J Neurosci 16:2508–2521

    CAS  PubMed  Google Scholar 

  227. Nakajima K, Tohyama Y, Kohsaka S, Kurihara T (2002) Ceramide activates microglia to enhance the production/secretion of brain-derived neurotrophic factor (BDNF) without induction of deleterious factors in vitro. J Neurochem 80:697–705

    CAS  PubMed  Google Scholar 

  228. Rabchevsky AG, Streit WJ (1997) Grafting of cultured microglial cells into the lesioned spinal cord of adult rats enhances neurite outgrowth. J Neurosci Res 47:34–48

    CAS  PubMed  Google Scholar 

  229. MacEwan DJ (2002) TNF ligands and receptors–a matter of life and death. Br J Pharmacol 135:855–875

    CAS  PubMed  Google Scholar 

  230. Choi YK, Kim KW (2008) Blood-neural barrier: its diversity and coordinated cell-to-cell communication. BMB Rep 41:345–352

    CAS  PubMed  Google Scholar 

  231. Willis CL (2011) Glia-induced reversible disruption of blood-brain barrier integrity and neuropathological response of the neurovascular unit. Toxicol Pathol 39:172–185

    PubMed  Google Scholar 

  232. Nishioku T, Matsumoto J, Dohgu S, Sumi N, Miyao K, Takata F, Shuto H, Yamauchi A, Kataoka Y (2010) Tumor necrosis factor-alpha mediates the blood-brain barrier dysfunction induced by activated microglia in mouse brain microvascular endothelial cells. J Pharmacol Sci 112:251–254

    CAS  PubMed  Google Scholar 

  233. Capoccia BJ, Gregory AD, Link DC (2008) Recruitment of the inflammatory subset of monocytes to sites of ischemia induces angiogenesis in a monocyte chemoattractant protein-1-dependent fashion. J Leukoc Biol 84:760–768

    CAS  PubMed  Google Scholar 

  234. Frangogiannis NG, Dewald O, Xia Y, Ren G, Haudek S, Leucker T, Kraemer D, Taffet G, Rollins BJ, Entman ML (2007) Critical role of monocyte chemoattractant protein-1/CC chemokine ligand 2 in the pathogenesis of ischemic cardiomyopathy. Circulation 115:584–592

    CAS  PubMed  Google Scholar 

  235. Kim GH, Kellner CP, Hahn DK, Desantis BM, Musabbir M, Starke RM, Rynkowski M, Komotar RJ, Otten ML, Sciacca R et al (2008) Monocyte chemoattractant protein-1 predicts outcome and vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg 109:38–43

    CAS  PubMed  Google Scholar 

  236. Morimoto H, Hirose M, Takahashi M, Kawaguchi M, Ise H, Kolattukudy PE, Yamada M, Ikeda U (2008) MCP-1 induces cardioprotection against ischaemia/reperfusion injury: role of reactive oxygen species. Cardiovasc Res 78:554–562

    CAS  PubMed  Google Scholar 

  237. Yan YP, Sailor KA, Lang BT, Park SW, Vemuganti R, Dempsey RJ (2007) Monocyte chemoattractant protein-1 plays a critical role in neuroblast migration after focal cerebral ischemia. J Cereb Blood Flow Metab 27:1213–1224

    CAS  PubMed  Google Scholar 

  238. Chen BP, Kuziel WA, Lane TE (2001) Lack of CCR2 results in increased mortality and impaired leukocyte activation and trafficking following infection of the central nervous system with a neurotropic coronavirus. J Immunol 167:4585–4592

    CAS  PubMed  Google Scholar 

  239. El Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C, Luster AD (2007) Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 13:432–438

    PubMed  Google Scholar 

  240. Galasso JM, Liu Y, Szaflarski J, Warren JS, Silverstein FS (2000) Monocyte chemoattractant protein-1 is a mediator of acute excitotoxic injury in neonatal rat brain. Neuroscience 101:737–744

    CAS  PubMed  Google Scholar 

  241. Tsirka SE, Gualandris A, Amaral DG, Strickland S (1995) Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. Nature 377:340–344

    CAS  PubMed  Google Scholar 

  242. Tsirka SE, Rogove AD, Bugge TH, Degen JL, Strickland S (1997) An extracellular proteolytic cascade promotes neuronal degeneration in the mouse hippocampus. J Neurosci 17:543–552

    CAS  PubMed  Google Scholar 

  243. Cho ML, Yoon BY, Ju JH, Jung YO, Jhun JY, Park MK, Park SH, Cho CS, Kim HY (2007) Expression of CCR2A, an isoform of MCP-1 receptor, is increased by MCP-1, CD40 ligand and TGF-beta in fibroblast like synoviocytes of patients with RA. Exp Mol Med 39:499–507

    CAS  PubMed  Google Scholar 

  244. Sanders SK, Crean SM, Boxer PA, Kellner D, LaRosa GJ, Hunt SW 3rd (2000) Functional differences between monocyte chemotactic protein-1 receptor A and monocyte chemotactic protein-1 receptor B expressed in a Jurkat T cell. J Immunol 165:4877–4883

    CAS  PubMed  Google Scholar 

  245. Proost P, Struyf S, Couvreur M, Lenaerts JP, Conings R, Menten P, Verhaert P, Wuyts A, Van Damme J (1998) Posttranslational modifications affect the activity of the human monocyte chemotactic proteins MCP-1 and MCP-2: identification of MCP-2(6-76) as a natural chemokine inhibitor. J Immunol 160:4034–4041

    CAS  PubMed  Google Scholar 

  246. Dean RA, Cox JH, Bellac CL, Doucet A, Starr AE, Overall CM (2008) Macrophage-specific metalloelastase (MMP-12) truncates and inactivates ELR+CXC chemokines and generates CCL2, -7, -8, and -13 antagonists: potential role of the macrophage in terminating polymorphonuclear leukocyte influx. Blood 112:3455–3464

    CAS  PubMed  Google Scholar 

  247. McQuibban GA, Gong JH, Wong JP, Wallace JL, Clark-Lewis I, Overall CM (2002) Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo. Blood 100:1160–1167

    CAS  PubMed  Google Scholar 

  248. Gong JH, Clark-Lewis I (1995) Antagonists of monocyte chemoattractant protein 1 identified by modification of functionally critical NH2-terminal residues. J Exp Med 181:631–640

    CAS  PubMed  Google Scholar 

  249. Kitamoto S, Egashira K (2003) Anti-monocyte chemoattractant protein-1 gene therapy for cardiovascular diseases. Expert Rev Cardiovasc Ther 1:393–400

    CAS  PubMed  Google Scholar 

  250. Ni W, Egashira K, Kitamoto S, Kataoka C, Koyanagi M, Inoue S, Imaizumi K, Akiyama C, Nishida KI, Takeshita A (2001) New anti-monocyte chemoattractant protein-1 gene therapy attenuates atherosclerosis in apolipoprotein E-knockout mice. Circulation 103:2096–2101

    CAS  PubMed  Google Scholar 

  251. Zlokovic BV (2008) The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 57:178–201

    CAS  PubMed  Google Scholar 

  252. Iadecola C (2004) Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci 5:347–360

    CAS  PubMed  Google Scholar 

  253. Ben-Menachem E, Johansson BB, Svensson TH (1982) Increased vulnerability of the blood-brain barrier to acute hypertension following depletion of brain noradrenaline. J Neural Transm 53:159–167

    CAS  PubMed  Google Scholar 

  254. Cohen Z, Bonvento G, Lacombe P, Hamel E (1996) Serotonin in the regulation of brain microcirculation. Prog Neurobiol 50:335–362

    CAS  PubMed  Google Scholar 

  255. Cohen Z, Molinatti G, Hamel E (1997) Astroglial and vascular interactions of noradrenaline terminals in the rat cerebral cortex. J Cereb Blood Flow Metab 17:894–904

    CAS  PubMed  Google Scholar 

  256. Hawkins BT, Davis TP (2005) The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 57:173–185

    CAS  PubMed  Google Scholar 

  257. Tong XK, Hamel E (1999) Regional cholinergic denervation of cortical microvessels and nitric oxide synthase-containing neurons in Alzheimer’s disease. Neuroscience 92:163–175

    CAS  PubMed  Google Scholar 

  258. Vaucher E, Hamel E (1995) Cholinergic basal forebrain neurons project to cortical microvessels in the rat: electron microscopic study with anterogradely transported Phaseolus vulgaris leucoagglutinin and choline acetyltransferase immunocytochemistry. J Neurosci 15:7427–7441

    CAS  PubMed  Google Scholar 

  259. Vaucher E, Tong XK, Cholet N, Lantin S, Hamel E (2000) GABA neurons provide a rich input to microvessels but not nitric oxide neurons in the rat cerebral cortex: a means for direct regulation of local cerebral blood flow. J Comp Neurol 421:161–171

    CAS  PubMed  Google Scholar 

  260. Minami M (2011) Neuro-glio-vascular interaction in ischemic brains. Yakugaku Zasshi 131:539–544

    CAS  PubMed  Google Scholar 

  261. Gosselin RD, Varela C, Banisadr G, Mechighel P, Rostene W, Kitabgi P, Melik-Parsadaniantz S (2005) Constitutive expression of CCR2 chemokine receptor and inhibition by MCP-1/CCL2 of GABA-induced currents in spinal cord neurones. J Neurochem 95:1023–1034

    CAS  PubMed  Google Scholar 

  262. Guo W, Wang H, Zou S, Dubner R, Ren K (2012) Chemokine signaling involving chemokine (C–C motif) ligand 2 plays a role in descending pain facilitation. Neurosci Bull 28:193–207

    CAS  PubMed  Google Scholar 

  263. Old EA, Malcangio M (2012) Chemokine mediated neuron-glia communication and aberrant signalling in neuropathic pain states. Curr Opin Pharmacol 12:67–73

    CAS  PubMed  Google Scholar 

  264. Zhang H, Boyette-Davis JA, Kosturakis AK, Li Y, Yoon SY, Walters ET, Dougherty PM (2013). Induction of monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2 in primary sensory neurons contributes to paclitaxel-induced peripheral neuropathy. J Pain (in press)

  265. Zhang ZJ, Dong YL, Lu Y, Cao S, Zhao ZQ, Gao YJ (2012) Chemokine CCL2 and its receptor CCR2 in the medullary dorsal horn are involved in trigeminal neuropathic pain. J Neuroinflammation 9:136

    CAS  PubMed Central  PubMed  Google Scholar 

  266. Godefroy D, Gosselin RD, Yasutake A, Fujimura M, Combadiere C, Maury-Brachet R, Laclau M, Rakwal R, Melik-Parsadaniantz S, Bourdineaud JP, Rostene W (2012) The chemokine CCL2 protects against methylmercury neurotoxicity. Toxicol Sci 125:209–218

    CAS  PubMed  Google Scholar 

  267. Stowe AM, Wacker BK, Cravens PD, Perfater JL, Li MK, Hu R, Freie AB, Stuve O, Gidday JM (2012) CCL2 upregulation triggers hypoxic preconditioning-induced protection from stroke. J Neuroinflammation 9:33

    CAS  PubMed Central  PubMed  Google Scholar 

  268. Schellenberg AE, Buist R, Del Bigio MR, Toft-Hansen H, Khorooshi R, Owens T, Peeling J (2012) Blood-brain barrier disruption in CCL2 transgenic mice during pertussis toxin-induced brain inflammation. Fluids Barriers CNS 9:10

    CAS  PubMed Central  PubMed  Google Scholar 

  269. Dimitrijevic OB, Stamatovic SM, Keep RF, Andjelkovic AV (2007) Absence of the chemokine receptor CCR2 protects against cerebral ischemia/reperfusion injury in mice. Stroke 38:1345–1353

    CAS  PubMed  Google Scholar 

  270. Yao Y, Tsirka SE (2012) The CCL2-CCR2 system affects the progression and clearance of intracerebral hemorrhage. Glia 60:908–918

    PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

We thank members of the Tsirka laboratory for discussions. This work was supported by NIH R01NS42168 (SET) and Sigma Xi Grant-in-Aid of Research (YY).

Author information

Authors and Affiliations

  1. Program in Molecular and Cellular Pharmacology, Department of Pharmacological Sciences, BST8-192, Stony Brook University, Stony Brook, NY, 11794-8651, USA

    Yao Yao & Stella E. Tsirka

  2. Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY, 10065, USA

    Yao Yao

Authors
  1. Yao Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stella E. Tsirka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stella E. Tsirka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yao, Y., Tsirka, S.E. Monocyte chemoattractant protein-1 and the blood–brain barrier. Cell. Mol. Life Sci. 71, 683–697 (2014). https://doi.org/10.1007/s00018-013-1459-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-013-1459-1

Keywords

Search

Navigation