nach oben

Inflammation Research

Erschienen in:

16.07.2019 | Review

Regulation of C-reactive protein conformation in inflammation

verfasst von: ZhenYu Yao, Yanmin Zhang, HaiBin Wu

Erschienen in: Inflammation Research | Ausgabe 10/2019

Einloggen, um Zugang zu erhalten

Abstract

C-reactive protein (CRP) is a non-specific diagnostic marker of inflammation and an evolutionarily conserved protein with roles in innate immune signaling. Natural CRP is composed of five identical globular subunits that form a pentamer, but the role of pentameric CRP (pCRP) during inflammatory pathogenesis remains controversial. Emerging evidence suggests that pCRP can be dissociated into monomeric CRP (mCRP) that has major roles in host defenses and inflammation. Here, we discuss our current knowledge of the dissociation mechanisms of pCRP and summarize the stepwise conformational transition model to mCRP to elucidate how CRP dissociation contributes to proinflammatory activity. These discussions will evoke new understanding of this ancient protein.

Shrive AK, Gheetham GM, Holden D, Myles DA, Turnell WG, Volanakis JE, Pepys MB, Bloomer AC, Greenhough TJ. Three dimensional structure of human C-reactive protein. Nat Struct Mol Biol. 1996;3:346–54. https://doi.org/10.1038/nsb0496-346.CrossRef

Potempa LA, Maldonado BA, Laurent P, Zemel ES, Gewurz H. Antigenic, electrophoretic and binding alterations of human C-reactive protein modified selectively in the absence of calcium. Mol Immunol. 1983;20:1165–75. https://doi.org/10.1016/0161-5890(83)90140-2.CrossRefPubMed

Potempa LA, Yao ZY, Ji SR, Filep JG, Wu Y. Solubilization and purification of recombinant modified C-reactive protein from inclusion bodies using reversible anhydride modification. Biophys Rep. 2015;1:18–33. https://doi.org/10.1007/s41048-015-0003-2.CrossRefPubMedPubMedCentral

Thompson D, Pepys MB, Wood SP. The physiological structure of human C-reactive protein and its complex with phosphocholine. Structure. 1999;7:169–77.CrossRef

Wu Y, Potempa LA, El Kebir D, Filep JG. C-reactive protein and inflammation: conformational changes affect function. Biol Chem. 2015;396:1181–97. https://doi.org/10.1515/hsz-2015-0149.CrossRefPubMed

Kresl JJ, Potempa LA, Anderson BE. Conversion of native oligomeric to a modified monomeric form of human C-reactive protein. Int J Biochem Cell Biol. 1998;30:1415–26. https://doi.org/10.1016/S1357-2725(98)00078-8.CrossRefPubMed

Ji SR, Wu Y, Zhu L, Potempa LA, Sheng FL, Lu W, Zhao J. Cell membranes and liposomes dissociate C-reactive protein (CRP) to form a new, biologically active structural intermediate: mCRP(m). FASEB J. 2007;21:284–94. https://doi.org/10.1096/fj.06-6722com.CrossRefPubMed

Ji SR, Wu Y, Potempa LA, Liang YH, Zhao J. Effect of modified C-reactive protein on complement activation: a possible complement regulatory role of modified or monomeric C-reactive protein in atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2006;26:935–41. https://doi.org/10.1161/01.atv.0000206211.21895.73.CrossRefPubMed

Ji SR, Ma L, Bai CJ, Shi JM, Li HY, Potempa LA, Filep JG, Zhao J, Wu Y. Monomeric C-reactive protein activates endothelial cells via interaction with lipid raft microdomains. FASEB J. 2009;23:1806–16. https://doi.org/10.1096/fj.08-116962.CrossRefPubMed

10.

Wang MY, Ji SR, Bai CJ, El Kebir D, Li HY, Shi JM, Zhu W, Costantino S, Zhou HH, Potempa LA, Zhao J, Filep JG, Wu Y. A redox switch in C-reactive protein modulates activation of endothelial cells. FASEB J. 2011;25:3186–96. https://doi.org/10.1096/fj.11-182741.CrossRefPubMed

11.

Braig D, Nero TL, Koch HG, Kaiser B, Wang X, Thiele JR, Morton CJ, Zeller J, Kiefer J, Potempa LA, Mellett NA, Miles LA, Du XJ, Meikle PJ, Huber-Lang M, Stark GB, Parker MW, Peter K, Eisenhardt SU. Transitional changes in the CRP structure lead to the exposure of proinflammatory binding sites. Nat Commun. 2017;8:14188. https://doi.org/10.1038/ncomms14188.CrossRefPubMedPubMedCentral

12.

Thiele JR, Habersberger J, Braig D, Schmidt Y, Goerendt K, Maurer V, Bannasch H, Scheichl A, Woollard KJ, von Dobschütz E. Dissociation of pentameric to monomeric C-reactive protein localizes and aggravates inflammation in vivo proof of a powerful proinflammatory mechanism and a new anti-inflammatory strategy. Circulation. 2014;130:35–50. https://doi.org/10.1161/CIRCULATIONAHA.113.007124.CrossRefPubMed

13.

Eisenhardt SU, Habersberger J, Murphy A, Chen YC, Woollard KJ, Bassler N, Qian H, von Zur Muhlen C, Hagemeyer CE, Ahrens I, Chin-Dusting J, Bobik A, Peter K. Dissociation of pentameric to monomeric C-reactive protein on activated platelets localizes inflammation to atherosclerotic plaques. Circ Res. 2009;105:128–37. https://doi.org/10.1161/CIRCRESAHA.108.190611.CrossRefPubMed

14.

Schwedler SB. Tubular staining of modified C-reactive protein in diabetic chronic kidney disease. Nephrol Dial Transplant. 2003;18:2300–7. https://doi.org/10.1093/ndt/gfg407.CrossRefPubMed

15.

Thiele JR, Zeller J, Bannasch H, Stark GB, Peter K, Eisenhardt SU. Targeting C-reactive protein in inflammatory disease by preventing conformational changes. Mediat Inflamm. 2015;2015:372432. https://doi.org/10.1155/2015/372432.CrossRef

16.

Li QY, Li HY, Fu G, Yu F, Wu Y, Zhao MH. Autoantibodies against C-reactive protein influence complement activation and clinical course in lupus nephritis. J Am Soc Nephrol. 2017;28:3044–54. https://doi.org/10.1681/ASN.2016070735.CrossRefPubMedPubMedCentral

17.

Crawford JR, Trial J, Nambi V, Hoogeveen RC, Taffet GE, Entman ML. Plasma levels of endothelial microparticles bearing monomeric C-reactive protein are increased in peripheral artery disease. J Cardiovasc Transl Res. 2016;9:184–93. https://doi.org/10.1007/s12265-016-9678-0.CrossRefPubMedPubMedCentral

18.

Zhang L, Li HY, Li W, Shen ZY, Wang YD, Ji SR, Wu Y. An ELISA assay for quantifying monomeric C-reactive protein in plasma. Front Immunol. 2018;9:511. https://doi.org/10.3389/fimmu.2018.00511.CrossRefPubMedPubMedCentral

19.

Mihlan M, Stippa S, Jozsi M, Zipfel PF. Monomeric CRP contributes to complement control in fluid phase and on cellular surfaces and increases phagocytosis by recruiting factor H. Cell Death Differ. 2009;16:1630–40. https://doi.org/10.1038/cdd.2009.103.CrossRefPubMed

20.

O’Flynn J, van der Pol P, Dixon KO, Prohaszka Z, Daha MR, van Kooten C. Monomeric C-reactive protein inhibits renal cell-directed complement activation mediated by properdin. Am J Physiol Renal Physiol. 2016;310:F1308–16. https://doi.org/10.1152/ajprenal.00645.2014.CrossRefPubMed

21.

Khreiss T, József L, Potempa LA, Filep JG. Conformational rearrangement in C-reactive protein is required for proinflammatory actions on human endothelial cells. Circulation. 2004;109:2016–22.CrossRefPubMed

22.

Venugopal SK, Devaraj S, Yuhanna I, Shaul P, Jialal I. Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation. 2002;106:1439–41. https://doi.org/10.1161/01.CIR.0000033116.22237.F9.CrossRefPubMed

23.

Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation. 2000;102:2165–8. https://doi.org/10.1161/01.CIR.102.18.2165.CrossRefPubMed

24.

Thiele JR, Habersberger J, Braig D, Schmidt Y, Goerendt K, Maurer V, Bannasch H, Scheichl A, Woollard KJ, von Dobschutz E, Kolodgie F, Virmani R, Stark GB, Peter K, Eisenhardt SU. Dissociation of pentameric to monomeric C-reactive protein localizes and aggravates inflammation: in vivo proof of a powerful proinflammatory mechanism and a new anti-inflammatory strategy. Circulation. 2014;130:35–50. https://doi.org/10.1161/CIRCULATIONAHA.113.007124.CrossRefPubMed

25.

Potempa LA, Siegel JN, Fedel BA, Potempa RT, Gewurz H. Expression, detection and assay of a neoantigen (Neo-CRP) associated with a free, human C-reactive protein subunit. Mol Immunol. 1987;24:531–41. https://doi.org/10.1016/0161-5890(87)90028-9.CrossRefPubMed

26.

Wang MS, Messersmith RE, Reed SM. Membrane curvature recognition by C-reactive protein using lipoprotein mimics. Soft Matter. 2012;8:7909–18. https://doi.org/10.1039/C2SM25779C.CrossRefPubMedPubMedCentral

27.

Poon IKH, Lucas CD, Rossi AG, Ravichandran KS. Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol. 2014;14:166–80.CrossRefPubMedPubMedCentral

28.

Habersberger J, Strang F, Scheichl A, Htun N, Bassler N, Merivirta RM, Diehl P, Krippner G, Meikle P, Eisenhardt SU, Meredith I, Peter K. Circulating microparticles generate and transport monomeric C-reactive protein in patients with myocardial infarction. Cardiovasc Res. 2012;96:64–72. https://doi.org/10.1093/cvr/cvs237.CrossRefPubMed

29.

Strang F, Scheichl A, Chen YC, Wang X, Htun NM, Bassler N, Eisenhardt SU, Habersberger J, Peter K. Amyloid plaques dissociate pentameric to monomeric C-reactive protein: a novel pathomechanism driving cortical inflammation in Alzheimer’s disease? Brain Pathol. 2012;22:337–46. https://doi.org/10.1111/j.1750-3639.2011.00539.x.CrossRefPubMed

30.

Khreiss T, József L, Hossain S, Chan JS, Potempa LA, Filep JG. Loss of pentameric symmetry of C-reactive protein is associated with delayed apoptosis of human neutrophils. J Biol Chem. 2002;277:40775–81. https://doi.org/10.1074/jbc.M205378200.CrossRefPubMed

31.

Zouki C, Haas B, Chan JS, Potempa LA, Filep JG. Loss of pentameric symmetry of C-reactive protein is associated with promotion of neutrophil-endothelial cell adhesion. J Immunol. 2001;167:5355–61. https://doi.org/10.4049/jimmunol.167.9.5355.CrossRefPubMed

32.

Heuertz RM, Schneider GP, Potempa LA, Webster RO. Native and modified C-reactive protein bind different receptors on human neutrophils. Int J Biochem Cell Biol. 2005;37:320–35. https://doi.org/10.1016/j.biocel.2004.07.002.CrossRefPubMed

33.

Khreiss T, Jozsef L, Potempa LA, Filep JG. Conformational rearrangement in C-reactive protein is required for proinflammatory actions on human endothelial cells. Circulation. 2004;109:2016–22. https://doi.org/10.1161/01.CIR.0000125527.41598.68.CrossRefPubMed

34.

Khreiss T, József L, Potempa LA, Filep JG. Opposing effects of C-reactive protein isoforms on shear-induced neutrophil-platelet adhesion and neutrophil aggregation in whole blood. Circulation. 2004;110:2713–20. https://doi.org/10.1161/01.CIR.0000146846.00816.DD.CrossRefPubMed

35.

Li HY, Wang J, Meng F, Jia ZK, Su Y, Bai QF, Lv LL, Ma FR, Potempa LA, Yan YB, Ji SR, Wu Y. An intrinsically disordered motif mediates diverse actions of monomeric C-reactive protein. J Biol Chem. 2016;291:8795–804. https://doi.org/10.1074/jbc.M115.695023.CrossRefPubMedPubMedCentral

36.

Kinoshita CM, Ying SC, Hugli TE, Siegel JN, Potempa LA, Jiang H, Houghten RA, Gewurz H. Elucidation of a protease-sensitive site involved in the binding of calcium to C-reactive protein. Biochemistry. 1989;28:9840–8.CrossRefPubMed

37.

Ying SC, Shephard E, De Beer FC, Siegel JN, Harris D, Gewurz BE, Fridkin M, Gewurz H. Localization of sequence-determined neoepitopes and neutrophil digestion fragments of C-reactive protein utilizing monoclonal antibodies and synthetic peptides. Mol Immunol. 1992;29:677–87.CrossRefPubMed

38.

Shephard EG, Beer SM, Anderson R, Strachan AF, Nel AE, de Beer FC. Generation of biologically active C-reactive protein peptides by a neutral protease on the membrane of phorbol myristate acetate-stimulated neutrophils. J Immunol. 1989;143:2974–81.PubMed

39.

Shephard EG, Anderson R, Rosen O, Myer, Fridkin M, Strachan AF, De Beer FC. Peptides generated from C-reactive protein by a neutrophil membrane protease. Amino acid sequence and effects of peptides on neutrophil oxidative metabolism and chemotaxis. J Immunol. 1990;145:1469–76.PubMed

40.

Heuertz RM, Ahmed N, Webster RO. Peptides derived from C-reactive protein inhibit neutrophil alveolitis. J Immunol. 1996;156:3412–7.PubMed

41.

El Kebir D, Zhang Y, Potempa LA, Wu Y, Fournier A, Filep JG. C-reactive protein-derived peptide 201-206 inhibits neutrophil adhesion to endothelial cells and platelets through CD32. J Leukoc Biol. 2011;90:1167–75. https://doi.org/10.1189/jlb.0111032.CrossRefPubMed

42.

Ji SR, Wu Y, Potempa LA, Qiu Q, Zhao J. Interactions of C-reactive protein with low-density lipoproteins: implications for an active role of modified C-reactive protein in atherosclerosis. Int J Biochem Cell Biol. 2006;38:648–61. https://doi.org/10.1016/j.biocel.2005.11.004.CrossRefPubMed

43.

Caprio V, Badimon L, Di Napoli M, Fang WH, Ferris GR, Guo B, Iemma RS, Liu D, Zeinolabediny Y, Slevin M. pCRP-mCRP dissociation mechanisms as potential targets for the development of small-molecule anti-inflammatory chemotherapeutics. Front Immunol. 2018;9:1089. https://doi.org/10.3389/fimmu.2018.01089.CrossRefPubMedPubMedCentral

44.

Li HY, Liu XL, Liu YT, Jia ZK, Filep JG, Potempa LA, Ji SR, Wu Y. Matrix sieving-enforced retrograde transcytosis regulates tissue accumulation of C-reactive protein. Cardiovasc Res. 2019;115:440–52. https://doi.org/10.1093/cvr/cvy181.CrossRefPubMed

45.

Jabs WJ, Lögering BA, Gerke P, Kreft B, Wolber EM, Klinger MHF, Fricke L, Steinhoff J. The kidney as a second site of human C-reactive protein formation in vivo. Eur J Immunol. 2003;33:152–61.CrossRefPubMed

46.

Ramage L, Proudfoot L, Guy K. Expression of C-reactive protein in human lung epithelial cells and upregulation by cytokines and carbon particles. Inhal Toxicol. 2004;16:607–13. https://doi.org/10.1080/08958370490464599.CrossRefPubMed

47.

Yasojima K, Schwab C, McGeer EG, McGeer PL. Human neurons generate C-reactive protein and amyloid P: upregulation in Alzheimer’s disease. Brain Res. 2000;887:80–9. https://doi.org/10.1016/s0006-8993(00)02970-x.CrossRefPubMed

48.

Calabro P, Chang DW, Willerson JT, Yeh ET. Release of C-reactive protein in response to inflammatory cytokines by human adipocytes: linking obesity to vascular inflammation. J Am Coll Cardiol. 2005;46:1112–3. https://doi.org/10.1016/j.jacc.2005.06.017.CrossRefPubMed

49.

Kuta AE, Baum LL. C-reactive protein is produced by a small number of normal human peripheral blood lymphocytes. J Exp Med. 1986;164:321–6. https://doi.org/10.1084/jem.164.1.321.CrossRefPubMed

50.

Bello-Perez M, Falco A, Medina R, Encinar JA, Novoa B, Perez L, Estepa A, Coll J. Structure and functionalities of the human C-reactive protein compared to the zebrafish multigene family of C-reactive-like proteins. Dev Comp Immunol. 2016. https://doi.org/10.1016/j.dci.2016.12.001.CrossRefPubMed

51.

Chen R, Qi J, Yuan H, Wu Y, Hu W, Xia C. Crystal structures for short-chain pentraxin from zebrafish demonstrate a cyclic trimer with new recognition and effector faces. J Struct Biol. 2015;189:259–68. https://doi.org/10.1016/j.jsb.2015.01.001.CrossRefPubMed

52.

Zhang L, Liu SH, Wright TT, Shen ZY, Li HY, Zhu W, Potempa LA, Ji SR, Szalai AJ, Wu Y. C-reactive protein directly suppresses Th1 cell differentiation and alleviates experimental autoimmune encephalomyelitis. J Immunol. 2015;194:5243–52. https://doi.org/10.4049/jimmunol.1402909.CrossRefPubMedPubMedCentral

53.

Pepys MB, Hirschfield GM, Tennent GA, Gallimore JR, Kahan MC, Bellotti V, Hawkins PN, Myers RM, Smith MD, Polara A, Cobb AJ, Ley SV, Aquilina JA, Robinson CV, Sharif I, Gray GA, Sabin CA, Jenvey MC, Kolstoe SE, Thompson D, Wood SP. Targeting C-reactive protein for the treatment of cardiovascular disease. Nature. 2006;440:1217–21. https://doi.org/10.1038/nature04672.CrossRefPubMed

Titel: Regulation of C-reactive protein conformation in inflammation
verfasst von: ZhenYu Yao
Yanmin Zhang
HaiBin Wu
Publikationsdatum: 16.07.2019
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 10/2019
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-019-01269-1

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Auf Antibiotika verzichten? Was bei unkomplizierter Zystitis hilft

15.05.2024 Harnwegsinfektionen Nachrichten

Welche Antibiotika darf man bei unkomplizierter Zystitis verwenden und wovon sollte man die Finger lassen? Welche pflanzlichen Präparate können helfen? Was taugt der zugelassene Impfstoff? Antworten vom Koordinator der frisch überarbeiteten S3-Leitlinie, Prof. Florian Wagenlehner.

Schadet Ärger den Gefäßen?

14.05.2024 Arteriosklerose Nachrichten

In einer Studie aus New York wirkte sich Ärger kurzfristig deutlich negativ auf die Endothelfunktion gesunder Probanden aus. Möglicherweise hat dies Einfluss auf die kardiovaskuläre Gesundheit.

Intervallfasten zur Regeneration des Herzmuskels?

14.05.2024 Herzinfarkt Nachrichten

Die Nahrungsaufnahme auf wenige Stunden am Tag zu beschränken, hat möglicherweise einen günstigen Einfluss auf die Prognose nach akutem ST-Hebungsinfarkt. Darauf deutet eine Studie an der Uniklinik in Halle an der Saale hin.

Klimaschutz beginnt bei der Wahl des Inhalators

14.05.2024 Klimawandel Podcast

Auch kleine Entscheidungen im Alltag einer Praxis können einen großen Beitrag zum Klimaschutz leisten. Die neue Leitlinie zur "klimabewussten Verordnung von Inhalativa" geht mit gutem Beispiel voran, denn der Wechsel vom klimaschädlichen Dosieraerosol zum Pulverinhalator spart viele Tonnen CO₂. Leitlinienautor PD Dr. Guido Schmiemann erklärt, warum nicht nur die Umwelt, sondern auch Patientinnen und Patienten davon profitieren.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 10/2019

Interactions between carboxypeptidase M and kinin B1 receptor in endothelial cells

Organ crosstalk: the potent roles of inflammation and fibrotic changes in the course of organ interactions

The increased T helper cells proliferation and inflammatory responses in patients with type 2 diabetes mellitus is suppressed by sitagliptin and vitamin D3 in vitro

MiR-138-5p exacerbates hypoxia/reperfusion-induced heart injury through the inactivation of SIRT1-PGC-1α

Immunoexpression of canonical Wnt and NF-κB signaling pathways in the temporomandibular joint of arthritic rats