Skip to main content
Erschienen in: Angiogenesis 2/2014

01.04.2014 | Original Paper

The inflammatory response of lymphatic endothelium

verfasst von: David Aebischer, Maria Iolyeva, Cornelia Halin

Erschienen in: Angiogenesis | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

Abstract

Lymphatic vessels have traditionally been regarded as a rather inert drainage system, which just passively transports fluids, leukocytes and antigen. However, it is becoming increasingly clear that the lymphatic vasculature is highly dynamic and plays a much more active role in inflammatory and immune processes. Tissue inflammation induces a rapid, stimulus-specific upregulation of chemokines and adhesion molecules in lymphatic endothelial cells and a proliferative expansion of the lymphatic network in the inflamed tissue and in draining lymph nodes. Moreover, increasing evidence suggests that inflammation-induced changes in the lymphatic vasculature have a profound impact on the course of inflammatory and immune responses, by modulating fluid drainage, leukocyte migration or the removal of inflammatory mediators from tissues. In this review we will summarize and discuss current knowledge of the inflammatory response of lymphatic endothelium and of inflammation-induced lymphangiogenesis and the current perspective on the overall functional significance of these processes.
Literatur
4.
Zurück zum Zitat Baluk P, Fuxe J, Hashizume H, Romano T, Lashnits E, Butz S, Vestweber D, Corada M, Molendini C, Dejana E, McDonald DM (2007) Functionally specialized junctions between endothelial cells of lymphatic vessels. J Exp Med 204(10):2349–2362. doi:10.1084/jem.20062596 PubMedCentralPubMed Baluk P, Fuxe J, Hashizume H, Romano T, Lashnits E, Butz S, Vestweber D, Corada M, Molendini C, Dejana E, McDonald DM (2007) Functionally specialized junctions between endothelial cells of lymphatic vessels. J Exp Med 204(10):2349–2362. doi:10.​1084/​jem.​20062596 PubMedCentralPubMed
6.
Zurück zum Zitat Detmar M, Brown LF, Claffey KP, Yeo KT, Kocher O, Jackman RW, Berse B, Dvorak HF (1994) Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis. J Exp Med 180(3):1141–1146PubMed Detmar M, Brown LF, Claffey KP, Yeo KT, Kocher O, Jackman RW, Berse B, Dvorak HF (1994) Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis. J Exp Med 180(3):1141–1146PubMed
7.
Zurück zum Zitat Wauke K, Nagashima M, Ishiwata T, Asano G, Yoshino S (2002) Expression and localization of vascular endothelial growth factor-C in rheumatoid arthritis synovial tissue. J Rheumatol 29(1):34–38PubMed Wauke K, Nagashima M, Ishiwata T, Asano G, Yoshino S (2002) Expression and localization of vascular endothelial growth factor-C in rheumatoid arthritis synovial tissue. J Rheumatol 29(1):34–38PubMed
8.
Zurück zum Zitat Pedica F, Ligorio C, Tonelli P, Bartolini S, Baccarini P (2008) Lymphangiogenesis in Crohn’s disease: an immunohistochemical study using monoclonal antibody D2-40. Virchows Arch 452(1):57–63. doi:10.1007/s00428-007-0540-2 PubMed Pedica F, Ligorio C, Tonelli P, Bartolini S, Baccarini P (2008) Lymphangiogenesis in Crohn’s disease: an immunohistochemical study using monoclonal antibody D2-40. Virchows Arch 452(1):57–63. doi:10.​1007/​s00428-007-0540-2 PubMed
9.
Zurück zum Zitat Nakano T, Nakashima Y, Yonemitsu Y, Sumiyoshi S, Chen YX, Akishima Y, Ishii T, Iida M, Sueishi K (2005) Angiogenesis and lymphangiogenesis and expression of lymphangiogenic factors in the atherosclerotic intima of human coronary arteries. Hum Pathol 36(4):330–340. doi:10.1016/j.humpath.2005.01.001 PubMed Nakano T, Nakashima Y, Yonemitsu Y, Sumiyoshi S, Chen YX, Akishima Y, Ishii T, Iida M, Sueishi K (2005) Angiogenesis and lymphangiogenesis and expression of lymphangiogenic factors in the atherosclerotic intima of human coronary arteries. Hum Pathol 36(4):330–340. doi:10.​1016/​j.​humpath.​2005.​01.​001 PubMed
10.
Zurück zum Zitat Baluk P, Tammela T, Ator E, Lyubynska N, Achen MG, Hicklin DJ, Jeltsch M, Petrova TV, Pytowski B, Stacker SA, Yla-Herttuala S, Jackson DG, Alitalo K, McDonald DM (2005) Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J Clin Invest 115(2):247–257. doi:10.1172/JCI22037 PubMedCentralPubMed Baluk P, Tammela T, Ator E, Lyubynska N, Achen MG, Hicklin DJ, Jeltsch M, Petrova TV, Pytowski B, Stacker SA, Yla-Herttuala S, Jackson DG, Alitalo K, McDonald DM (2005) Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J Clin Invest 115(2):247–257. doi:10.​1172/​JCI22037 PubMedCentralPubMed
11.
Zurück zum Zitat Kerjaschki D, Huttary N, Raab I, Regele H, Bojarski-Nagy K, Bartel G, Krober SM, Greinix H, Rosenmaier A, Karlhofer F, Wick N, Mazal PR (2006) Lymphatic endothelial progenitor cells contribute to de novo lymphangiogenesis in human renal transplants. Nat Med 12(2):230–234. doi:10.1038/nm1340 PubMed Kerjaschki D, Huttary N, Raab I, Regele H, Bojarski-Nagy K, Bartel G, Krober SM, Greinix H, Rosenmaier A, Karlhofer F, Wick N, Mazal PR (2006) Lymphatic endothelial progenitor cells contribute to de novo lymphangiogenesis in human renal transplants. Nat Med 12(2):230–234. doi:10.​1038/​nm1340 PubMed
12.
Zurück zum Zitat Dashkevich A, Heilmann C, Kayser G, Germann M, Beyersdorf F, Passlick B, Geissler HJ (2010) Lymph angiogenesis after lung transplantation and relation to acute organ rejection in humans. Ann Thorac Surg 90(2):406–411. doi:10.1016/j.athoracsur.2010.03.013 PubMed Dashkevich A, Heilmann C, Kayser G, Germann M, Beyersdorf F, Passlick B, Geissler HJ (2010) Lymph angiogenesis after lung transplantation and relation to acute organ rejection in humans. Ann Thorac Surg 90(2):406–411. doi:10.​1016/​j.​athoracsur.​2010.​03.​013 PubMed
14.
Zurück zum Zitat Guo R, Zhou Q, Proulx ST, Wood R, Ji RC, Ritchlin CT, Pytowski B, Zhu Z, Wang YJ, Schwarz EM, Xing L (2009) Inhibition of lymphangiogenesis and lymphatic drainage via vascular endothelial growth factor receptor 3 blockade increases the severity of inflammation in a mouse model of chronic inflammatory arthritis. Arthritis Rheum 60(9):2666–2676. doi:10.1002/art.24764 PubMedCentralPubMed Guo R, Zhou Q, Proulx ST, Wood R, Ji RC, Ritchlin CT, Pytowski B, Zhu Z, Wang YJ, Schwarz EM, Xing L (2009) Inhibition of lymphangiogenesis and lymphatic drainage via vascular endothelial growth factor receptor 3 blockade increases the severity of inflammation in a mouse model of chronic inflammatory arthritis. Arthritis Rheum 60(9):2666–2676. doi:10.​1002/​art.​24764 PubMedCentralPubMed
15.
16.
Zurück zum Zitat Chen L, Hamrah P, Cursiefen C, Zhang Q, Pytowski B, Streilein JW, Dana MR (2004) Vascular endothelial growth factor receptor-3 mediates induction of corneal alloimmunity. Nat Med 10(8):813–815. doi:10.1038/nm1078 PubMed Chen L, Hamrah P, Cursiefen C, Zhang Q, Pytowski B, Streilein JW, Dana MR (2004) Vascular endothelial growth factor receptor-3 mediates induction of corneal alloimmunity. Nat Med 10(8):813–815. doi:10.​1038/​nm1078 PubMed
17.
Zurück zum Zitat Dietrich T, Bock F, Yuen D, Hos D, Bachmann BO, Zahn G, Wiegand S, Chen L, Cursiefen C (2010) Cutting edge: lymphatic vessels, not blood vessels, primarily mediate immune rejections after transplantation. J Immunol 184(2):535–539. doi:10.4049/jimmunol.0903180 PubMed Dietrich T, Bock F, Yuen D, Hos D, Bachmann BO, Zahn G, Wiegand S, Chen L, Cursiefen C (2010) Cutting edge: lymphatic vessels, not blood vessels, primarily mediate immune rejections after transplantation. J Immunol 184(2):535–539. doi:10.​4049/​jimmunol.​0903180 PubMed
18.
Zurück zum Zitat Nykanen AI, Sandelin H, Krebs R, Keranen MA, Tuuminen R, Karpanen T, Wu Y, Pytowski B, Koskinen PK, Yla-Herttuala S, Alitalo K, Lemstrom KB (2010) Targeting lymphatic vessel activation and CCL21 production by vascular endothelial growth factor receptor-3 inhibition has novel immunomodulatory and antiarteriosclerotic effects in cardiac allografts. Circulation 121(12):1413–1422. doi:10.1161/CIRCULATIONAHA.109.910703 PubMed Nykanen AI, Sandelin H, Krebs R, Keranen MA, Tuuminen R, Karpanen T, Wu Y, Pytowski B, Koskinen PK, Yla-Herttuala S, Alitalo K, Lemstrom KB (2010) Targeting lymphatic vessel activation and CCL21 production by vascular endothelial growth factor receptor-3 inhibition has novel immunomodulatory and antiarteriosclerotic effects in cardiac allografts. Circulation 121(12):1413–1422. doi:10.​1161/​CIRCULATIONAHA.​109.​910703 PubMed
20.
21.
Zurück zum Zitat Cohen JN, Guidi CJ, Tewalt EF, Qiao H, Rouhani SJ, Ruddell A, Farr AG, Tung KS, Engelhard VH (2010) Lymph node-resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation. J Exp Med 207(4):681–688PubMedCentralPubMed Cohen JN, Guidi CJ, Tewalt EF, Qiao H, Rouhani SJ, Ruddell A, Farr AG, Tung KS, Engelhard VH (2010) Lymph node-resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation. J Exp Med 207(4):681–688PubMedCentralPubMed
22.
Zurück zum Zitat Tewalt EF, Cohen JN, Rouhani SJ, Guidi CJ, Qiao H, Fahl SP, Conaway MR, Bender TP, Tung KS, Vella AT, Adler AJ, Chen L, Engelhard VH (2012) Lymphatic endothelial cells induce tolerance via PD-L1 and lack of costimulation leading to high-level PD-1 expression on CD8 T cells. Blood 120(24):4772–4782. doi:10.1182/blood-2012-04-427013 PubMedCentralPubMed Tewalt EF, Cohen JN, Rouhani SJ, Guidi CJ, Qiao H, Fahl SP, Conaway MR, Bender TP, Tung KS, Vella AT, Adler AJ, Chen L, Engelhard VH (2012) Lymphatic endothelial cells induce tolerance via PD-L1 and lack of costimulation leading to high-level PD-1 expression on CD8 T cells. Blood 120(24):4772–4782. doi:10.​1182/​blood-2012-04-427013 PubMedCentralPubMed
26.
Zurück zum Zitat Cursiefen C, Chen L, Borges LP, Jackson D, Cao J, Radziejewski C, D’Amore PA, Dana MR, Wiegand SJ, Streilein JW (2004) VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J Clin Invest 113(7):1040–1050. doi:10.1172/JCI20465 PubMedCentralPubMed Cursiefen C, Chen L, Borges LP, Jackson D, Cao J, Radziejewski C, D’Amore PA, Dana MR, Wiegand SJ, Streilein JW (2004) VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J Clin Invest 113(7):1040–1050. doi:10.​1172/​JCI20465 PubMedCentralPubMed
27.
Zurück zum Zitat Kataru RP, Jung K, Jang C, Yang H, Schwendener RA, Baik JE, Han SH, Alitalo K, Koh GY (2009) Critical role of CD11b+ macrophages and VEGF in inflammatory lymphangiogenesis, antigen clearance, and inflammation resolution. Blood 113(22):5650–5659. doi:10.1182/blood-2008-09-176776 PubMed Kataru RP, Jung K, Jang C, Yang H, Schwendener RA, Baik JE, Han SH, Alitalo K, Koh GY (2009) Critical role of CD11b+ macrophages and VEGF in inflammatory lymphangiogenesis, antigen clearance, and inflammation resolution. Blood 113(22):5650–5659. doi:10.​1182/​blood-2008-09-176776 PubMed
28.
Zurück zum Zitat Kim KE, Koh YJ, Jeon BH, Jang C, Han J, Kataru RP, Schwendener RA, Kim JM, Koh GY (2009) Role of CD11b+ macrophages in intraperitoneal lipopolysaccharide-induced aberrant lymphangiogenesis and lymphatic function in the diaphragm. Am J Pathol 175(4):1733–1745. doi:10.2353/ajpath.2009.090133 PubMedCentralPubMed Kim KE, Koh YJ, Jeon BH, Jang C, Han J, Kataru RP, Schwendener RA, Kim JM, Koh GY (2009) Role of CD11b+ macrophages in intraperitoneal lipopolysaccharide-induced aberrant lymphangiogenesis and lymphatic function in the diaphragm. Am J Pathol 175(4):1733–1745. doi:10.​2353/​ajpath.​2009.​090133 PubMedCentralPubMed
29.
Zurück zum Zitat Maruyama K, Ii M, Cursiefen C, Jackson DG, Keino H, Tomita M, Van Rooijen N, Takenaka H, D’Amore PA, Stein-Streilein J, Losordo DW, Streilein JW (2005) Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages. J Clin Invest 115(9):2363–2372. doi:10.1172/JCI23874 PubMedCentralPubMed Maruyama K, Ii M, Cursiefen C, Jackson DG, Keino H, Tomita M, Van Rooijen N, Takenaka H, D’Amore PA, Stein-Streilein J, Losordo DW, Streilein JW (2005) Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages. J Clin Invest 115(9):2363–2372. doi:10.​1172/​JCI23874 PubMedCentralPubMed
30.
Zurück zum Zitat Furtado GC, Marinkovic T, Martin AP, Garin A, Hoch B, Hubner W, Chen BK, Genden E, Skobe M, Lira SA (2007) Lymphotoxin beta receptor signaling is required for inflammatory lymphangiogenesis in the thyroid. Proc Natl Acad Sci USA 104(12):5026–5031. doi:10.1073/pnas.0606697104 PubMedCentralPubMed Furtado GC, Marinkovic T, Martin AP, Garin A, Hoch B, Hubner W, Chen BK, Genden E, Skobe M, Lira SA (2007) Lymphotoxin beta receptor signaling is required for inflammatory lymphangiogenesis in the thyroid. Proc Natl Acad Sci USA 104(12):5026–5031. doi:10.​1073/​pnas.​0606697104 PubMedCentralPubMed
33.
Zurück zum Zitat Choi I, Lee YS, Chung HK, Choi D, Ecoiffier T, Lee HN, Kim KE, Lee S, Park EK, Maeng YS, Kim NY, Ladner RD, Petasis NA, Koh CJ, Chen L, Lenz HJ, Hong YK (2013) Interleukin-8 reduces post-surgical lymphedema formation by promoting lymphatic vessel regeneration. Angiogenesis 16(1):29–44. doi:10.1007/s10456-012-9297-6 PubMed Choi I, Lee YS, Chung HK, Choi D, Ecoiffier T, Lee HN, Kim KE, Lee S, Park EK, Maeng YS, Kim NY, Ladner RD, Petasis NA, Koh CJ, Chen L, Lenz HJ, Hong YK (2013) Interleukin-8 reduces post-surgical lymphedema formation by promoting lymphatic vessel regeneration. Angiogenesis 16(1):29–44. doi:10.​1007/​s10456-012-9297-6 PubMed
35.
Zurück zum Zitat Chaitanya GV, Franks SE, Cromer W, Wells SR, Bienkowska M, Jennings MH, Ruddell A, Ando T, Wang Y, Gu Y, Sapp M, Mathis JM, Jordan PA, Minagar A, Alexander JS (2010) Differential cytokine responses in human and mouse lymphatic endothelial cells to cytokines in vitro. Lymphat Res Biol 8(3):155–164. doi:10.1089/lrb.2010.0004 PubMedCentralPubMed Chaitanya GV, Franks SE, Cromer W, Wells SR, Bienkowska M, Jennings MH, Ruddell A, Ando T, Wang Y, Gu Y, Sapp M, Mathis JM, Jordan PA, Minagar A, Alexander JS (2010) Differential cytokine responses in human and mouse lymphatic endothelial cells to cytokines in vitro. Lymphat Res Biol 8(3):155–164. doi:10.​1089/​lrb.​2010.​0004 PubMedCentralPubMed
37.
Zurück zum Zitat Oka M, Iwata C, Suzuki HI, Kiyono K, Morishita Y, Watabe T, Komuro A, Kano MR, Miyazono K (2008) Inhibition of endogenous TGF-beta signaling enhances lymphangiogenesis. Blood 111(9):4571–4579. doi:10.1182/blood-2007-10-120337 PubMed Oka M, Iwata C, Suzuki HI, Kiyono K, Morishita Y, Watabe T, Komuro A, Kano MR, Miyazono K (2008) Inhibition of endogenous TGF-beta signaling enhances lymphangiogenesis. Blood 111(9):4571–4579. doi:10.​1182/​blood-2007-10-120337 PubMed
39.
40.
Zurück zum Zitat Vigl B, Aebischer D, Nitschke M, Iolyeva M, Rothlin T, Antsiferova O, Halin C (2011) Tissue inflammation modulates gene expression of lymphatic endothelial cells and dendritic cell migration in a stimulus-dependent manner. Blood 118(1):205–215. doi:10.1182/blood-2010-12-326447 PubMed Vigl B, Aebischer D, Nitschke M, Iolyeva M, Rothlin T, Antsiferova O, Halin C (2011) Tissue inflammation modulates gene expression of lymphatic endothelial cells and dendritic cell migration in a stimulus-dependent manner. Blood 118(1):205–215. doi:10.​1182/​blood-2010-12-326447 PubMed
41.
Zurück zum Zitat Pegu A, Qin S, Fallert Junecko BA, Nisato RE, Pepper MS, Reinhart TA (2008) Human lymphatic endothelial cells express multiple functional TLRs. J Immunol 180(5):3399–3405PubMed Pegu A, Qin S, Fallert Junecko BA, Nisato RE, Pepper MS, Reinhart TA (2008) Human lymphatic endothelial cells express multiple functional TLRs. J Immunol 180(5):3399–3405PubMed
42.
Zurück zum Zitat Martln-Fontecha A, Sebastiani S, Hopken UE, Uguccioni M, Lipp M, Lanzavecchia A, Sallusto F (2003) Regulation of dendritic cell migration to the draining lymph node: impact on T lymphocyte traffic and priming. J Exp Med 198(4):615–621 Martln-Fontecha A, Sebastiani S, Hopken UE, Uguccioni M, Lipp M, Lanzavecchia A, Sallusto F (2003) Regulation of dendritic cell migration to the draining lymph node: impact on T lymphocyte traffic and priming. J Exp Med 198(4):615–621
43.
Zurück zum Zitat Brown MN, Fintushel SR, Lee MH, Jennrich S, Geherin SA, Hay JB, Butcher EC, Debes GF (2010) Chemoattractant receptors and lymphocyte egress from extralymphoid tissue: changing requirements during the course of inflammation. J Immunol 185(8):4873–4882. doi:10.4049/jimmunol.1000676 PubMedCentralPubMed Brown MN, Fintushel SR, Lee MH, Jennrich S, Geherin SA, Hay JB, Butcher EC, Debes GF (2010) Chemoattractant receptors and lymphocyte egress from extralymphoid tissue: changing requirements during the course of inflammation. J Immunol 185(8):4873–4882. doi:10.​4049/​jimmunol.​1000676 PubMedCentralPubMed
45.
Zurück zum Zitat Maddaluno L, Verbrugge SE, Martinoli C, Matteoli G, Chiavelli A, Zeng Y, Williams ED, Rescigno M, Cavallaro U (2009) The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells. J Exp Med 206(3):623–635. doi:10.1084/jem.20081211 PubMedCentralPubMed Maddaluno L, Verbrugge SE, Martinoli C, Matteoli G, Chiavelli A, Zeng Y, Williams ED, Rescigno M, Cavallaro U (2009) The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells. J Exp Med 206(3):623–635. doi:10.​1084/​jem.​20081211 PubMedCentralPubMed
46.
Zurück zum Zitat Iolyeva M, Karaman S, Willrodt AH, Weingartner S, Vigl B, Halin C (2013) Novel role for ALCAM in lymphatic network formation and function. FASEB J 27:978–990. doi:10.1096/fj.12-217844 PubMed Iolyeva M, Karaman S, Willrodt AH, Weingartner S, Vigl B, Halin C (2013) Novel role for ALCAM in lymphatic network formation and function. FASEB J 27:978–990. doi:10.​1096/​fj.​12-217844 PubMed
47.
Zurück zum Zitat Vigl B, Zgraggen C, Rehman N, Banziger-Tobler NE, Detmar M, Halin C (2009) Coxsackie-and adenovirus receptor (CAR) is expressed in lymphatic vessels in human skin and affects lymphatic endothelial cell function in vitro. Exp Cell Res 315(2):336–347. doi:10.1016/j.yexcr.2008.10.020 PubMed Vigl B, Zgraggen C, Rehman N, Banziger-Tobler NE, Detmar M, Halin C (2009) Coxsackie-and adenovirus receptor (CAR) is expressed in lymphatic vessels in human skin and affects lymphatic endothelial cell function in vitro. Exp Cell Res 315(2):336–347. doi:10.​1016/​j.​yexcr.​2008.​10.​020 PubMed
48.
Zurück zum Zitat Teijeira A, Garasa S, Pelaez R, Azpilikueta A, Ochoa C, Marre D, Rodrigues M, Alfaro C, Auba C, Valitutti S, Melero I, Rouzaut A (2013) Lymphatic endothelium forms integrin-engaging 3D structures during DC transit across inflamed lymphatic vessels. J Investig Dermatol. doi:10.1038/jid.2013.152 PubMed Teijeira A, Garasa S, Pelaez R, Azpilikueta A, Ochoa C, Marre D, Rodrigues M, Alfaro C, Auba C, Valitutti S, Melero I, Rouzaut A (2013) Lymphatic endothelium forms integrin-engaging 3D structures during DC transit across inflamed lymphatic vessels. J Investig Dermatol. doi:10.​1038/​jid.​2013.​152 PubMed
49.
Zurück zum Zitat Nitschke M, Aebischer D, Abadier M, Haener S, Lucic M, Vigl B, Luche H, Fehling HJ, Biehlmaier O, Lyck R, Halin C (2012) Differential requirement for ROCK in dendritic cell migration within lymphatic capillaries in steady-state and inflammation. Blood 120(11):2249–2258. doi:10.1182/blood-2012-03-417923 PubMed Nitschke M, Aebischer D, Abadier M, Haener S, Lucic M, Vigl B, Luche H, Fehling HJ, Biehlmaier O, Lyck R, Halin C (2012) Differential requirement for ROCK in dendritic cell migration within lymphatic capillaries in steady-state and inflammation. Blood 120(11):2249–2258. doi:10.​1182/​blood-2012-03-417923 PubMed
50.
Zurück zum Zitat Lammermann T, Bader BL, Monkley SJ, Worbs T, Wedlich-Soldner R, Hirsch K, Keller M, Forster R, Critchley DR, Fassler R, Sixt M (2008) Rapid leukocyte migration by integrin-independent flowing and squeezing. Nature 453(7191):51–55. doi:10.1038/nature06887 PubMed Lammermann T, Bader BL, Monkley SJ, Worbs T, Wedlich-Soldner R, Hirsch K, Keller M, Forster R, Critchley DR, Fassler R, Sixt M (2008) Rapid leukocyte migration by integrin-independent flowing and squeezing. Nature 453(7191):51–55. doi:10.​1038/​nature06887 PubMed
51.
Zurück zum Zitat Podgrabinska S, Kamalu O, Mayer L, Shimaoka M, Snoeck H, Randolph GJ, Skobe M (2009) Inflamed lymphatic endothelium suppresses dendritic cell maturation and function via Mac-1/ICAM-1-dependent mechanism. J Immunol 183(3):1767–1779. doi:10.4049/jimmunol.0802167 PubMed Podgrabinska S, Kamalu O, Mayer L, Shimaoka M, Snoeck H, Randolph GJ, Skobe M (2009) Inflamed lymphatic endothelium suppresses dendritic cell maturation and function via Mac-1/ICAM-1-dependent mechanism. J Immunol 183(3):1767–1779. doi:10.​4049/​jimmunol.​0802167 PubMed
52.
Zurück zum Zitat Issa A, Le TX, Shoushtari AN, Shields JD, Swartz MA (2009) Vascular endothelial growth factor-C and CC chemokine receptor 7 in tumor cell-lymphatic cross-talk promote invasive phenotype. Cancer Res 69(1):349–357. doi:10.1158/0008-5472.CAN-08-1875 PubMed Issa A, Le TX, Shoushtari AN, Shields JD, Swartz MA (2009) Vascular endothelial growth factor-C and CC chemokine receptor 7 in tumor cell-lymphatic cross-talk promote invasive phenotype. Cancer Res 69(1):349–357. doi:10.​1158/​0008-5472.​CAN-08-1875 PubMed
53.
54.
Zurück zum Zitat Weber M, Hauschild R, Schwarz J, Moussion C, de Vries I, Legler DF, Luther SA, Bollenbach T, Sixt M (2013) Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science 339(6117):328–332. doi:10.1126/science.1228456 PubMed Weber M, Hauschild R, Schwarz J, Moussion C, de Vries I, Legler DF, Luther SA, Bollenbach T, Sixt M (2013) Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science 339(6117):328–332. doi:10.​1126/​science.​1228456 PubMed
55.
Zurück zum Zitat Johnson LA, Jackson DG (2010) Inflammation-induced secretion of CCL21 in lymphatic endothelium is a key regulator of integrin-mediated dendritic cell transmigration. Int Immunol 22(10):839–849. doi:10.1093/intimm/dxq435 PubMed Johnson LA, Jackson DG (2010) Inflammation-induced secretion of CCL21 in lymphatic endothelium is a key regulator of integrin-mediated dendritic cell transmigration. Int Immunol 22(10):839–849. doi:10.​1093/​intimm/​dxq435 PubMed
56.
Zurück zum Zitat Beauvillain C, Cunin P, Doni A, Scotet M, Jaillon S, Loiry ML, Magistrelli G, Masternak K, Chevailler A, Delneste Y, Jeannin P (2011) CCR7 is involved in the migration of neutrophils to lymph nodes. Blood 117(4):1196–1204. doi:10.1182/blood-2009-11-254490 PubMed Beauvillain C, Cunin P, Doni A, Scotet M, Jaillon S, Loiry ML, Magistrelli G, Masternak K, Chevailler A, Delneste Y, Jeannin P (2011) CCR7 is involved in the migration of neutrophils to lymph nodes. Blood 117(4):1196–1204. doi:10.​1182/​blood-2009-11-254490 PubMed
57.
Zurück zum Zitat Kabashima K, Shiraishi N, Sugita K, Mori T, Onoue A, Kobayashi M, Sakabe J, Yoshiki R, Tamamura H, Fujii N, Inaba K, Tokura Y (2007) CXCL12-CXCR4 engagement is required for migration of cutaneous dendritic cells. Am J Pathol 171(4):1249–1257. doi:10.2353/ajpath.2007.070225 PubMedCentralPubMed Kabashima K, Shiraishi N, Sugita K, Mori T, Onoue A, Kobayashi M, Sakabe J, Yoshiki R, Tamamura H, Fujii N, Inaba K, Tokura Y (2007) CXCL12-CXCR4 engagement is required for migration of cutaneous dendritic cells. Am J Pathol 171(4):1249–1257. doi:10.​2353/​ajpath.​2007.​070225 PubMedCentralPubMed
59.
60.
Zurück zum Zitat Nielsen SR, Hammer T, Gibsona J, Pepperb MS, Nisatoc RE, Dissinga S, Tritsarisa K (2013) IL-27 inhibits lymphatic endothelial cell proliferation by STAT1-regulated gene expression. Microcirculation. doi:10.1111/micc.12055 PubMed Nielsen SR, Hammer T, Gibsona J, Pepperb MS, Nisatoc RE, Dissinga S, Tritsarisa K (2013) IL-27 inhibits lymphatic endothelial cell proliferation by STAT1-regulated gene expression. Microcirculation. doi:10.​1111/​micc.​12055 PubMed
61.
Zurück zum Zitat Kang S, Lee SP, Kim KE, Kim HZ, Memet S, Koh GY (2009) Toll-like receptor 4 in lymphatic endothelial cells contributes to LPS-induced lymphangiogenesis by chemotactic recruitment of macrophages. Blood 113(11):2605–2613. doi:10.1182/blood-2008-07-166934 PubMed Kang S, Lee SP, Kim KE, Kim HZ, Memet S, Koh GY (2009) Toll-like receptor 4 in lymphatic endothelial cells contributes to LPS-induced lymphangiogenesis by chemotactic recruitment of macrophages. Blood 113(11):2605–2613. doi:10.​1182/​blood-2008-07-166934 PubMed
62.
Zurück zum Zitat Garrafa E, Imberti L, Tiberio G, Prandini A, Giulini SM, Caimi L (2011) Heterogeneous expression of toll-like receptors in lymphatic endothelial cells derived from different tissues. Immunol Cell Biol 89(3):475–481. doi:10.1038/icb.2010.111 PubMed Garrafa E, Imberti L, Tiberio G, Prandini A, Giulini SM, Caimi L (2011) Heterogeneous expression of toll-like receptors in lymphatic endothelial cells derived from different tissues. Immunol Cell Biol 89(3):475–481. doi:10.​1038/​icb.​2010.​111 PubMed
63.
Zurück zum Zitat Johnson LA, Prevo R, Clasper S, Jackson DG (2007) Inflammation-induced uptake and degradation of the lymphatic endothelial hyaluronan receptor LYVE-1. J Biol Chem 282(46):33671–33680. doi:10.1093/intimm/dxq435 PubMed Johnson LA, Prevo R, Clasper S, Jackson DG (2007) Inflammation-induced uptake and degradation of the lymphatic endothelial hyaluronan receptor LYVE-1. J Biol Chem 282(46):33671–33680. doi:10.​1093/​intimm/​dxq435 PubMed
64.
Zurück zum Zitat Hou WH, Liu IH, Tsai CC, Johnson FE, Huang SS, Huang JS (2011) CRSBP-1/LYVE-1 ligands disrupt lymphatic intercellular adhesion by inducing tyrosine phosphorylation and internalization of VE-cadherin. J Cell Sci 124(Pt 8):1231–1244. doi:10.1242/jcs.078154 PubMedCentralPubMed Hou WH, Liu IH, Tsai CC, Johnson FE, Huang SS, Huang JS (2011) CRSBP-1/LYVE-1 ligands disrupt lymphatic intercellular adhesion by inducing tyrosine phosphorylation and internalization of VE-cadherin. J Cell Sci 124(Pt 8):1231–1244. doi:10.​1242/​jcs.​078154 PubMedCentralPubMed
65.
Zurück zum Zitat Platonova N, Miquel G, Regenfuss B, Taouji S, Cursiefen C, Chevet E, Bikfalvi A (2013) Evidence for the interaction of fibroblast growth factor-2 with the lymphatic endothelial cell marker LYVE-1. Blood 121(7):1229–1237. doi:10.1182/blood-2012-08-450502 PubMed Platonova N, Miquel G, Regenfuss B, Taouji S, Cursiefen C, Chevet E, Bikfalvi A (2013) Evidence for the interaction of fibroblast growth factor-2 with the lymphatic endothelial cell marker LYVE-1. Blood 121(7):1229–1237. doi:10.​1182/​blood-2012-08-450502 PubMed
66.
67.
Zurück zum Zitat Kunstfeld R, Hirakawa S, Hong YK, Schacht V, Lange-Asschenfeldt B, Velasco P, Lin C, Fiebiger E, Wei X, Wu Y, Hicklin D, Bohlen P, Detmar M (2004) Induction of cutaneous delayed-type hypersensitivity reactions in VEGF-A transgenic mice results in chronic skin inflammation associated with persistent lymphatic hyperplasia. Blood 104(4):1048–1057. doi:10.1182/blood-2003-08-2964 PubMed Kunstfeld R, Hirakawa S, Hong YK, Schacht V, Lange-Asschenfeldt B, Velasco P, Lin C, Fiebiger E, Wei X, Wu Y, Hicklin D, Bohlen P, Detmar M (2004) Induction of cutaneous delayed-type hypersensitivity reactions in VEGF-A transgenic mice results in chronic skin inflammation associated with persistent lymphatic hyperplasia. Blood 104(4):1048–1057. doi:10.​1182/​blood-2003-08-2964 PubMed
69.
Zurück zum Zitat Angeli V, Ginhoux F, Llodra J, Quemeneur L, Frenette PS, Skobe M, Jessberger R, Merad M, Randolph GJ (2006) B cell-driven lymphangiogenesis in inflamed lymph nodes enhances dendritic cell mobilization. Immunity 24(2):203–215. doi:10.1016/j.immuni.2006.01.003 PubMed Angeli V, Ginhoux F, Llodra J, Quemeneur L, Frenette PS, Skobe M, Jessberger R, Merad M, Randolph GJ (2006) B cell-driven lymphangiogenesis in inflamed lymph nodes enhances dendritic cell mobilization. Immunity 24(2):203–215. doi:10.​1016/​j.​immuni.​2006.​01.​003 PubMed
70.
Zurück zum Zitat Tan KW, Yeo KP, Wong FH, Lim HY, Khoo KL, Abastado JP, Angeli V (2012) Expansion of cortical and medullary sinuses restrains lymph node hypertrophy during prolonged inflammation. J Immunol 188(8):4065–4080. doi:10.4049/jimmunol.1101854 PubMed Tan KW, Yeo KP, Wong FH, Lim HY, Khoo KL, Abastado JP, Angeli V (2012) Expansion of cortical and medullary sinuses restrains lymph node hypertrophy during prolonged inflammation. J Immunol 188(8):4065–4080. doi:10.​4049/​jimmunol.​1101854 PubMed
71.
Zurück zum Zitat Nagy JA, Vasile E, Feng D, Sundberg C, Brown LF, Detmar MJ, Lawitts JA, Benjamin L, Tan X, Manseau EJ, Dvorak AM, Dvorak HF (2002) Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. J Exp Med 196(11):1497–1506PubMedCentralPubMed Nagy JA, Vasile E, Feng D, Sundberg C, Brown LF, Detmar MJ, Lawitts JA, Benjamin L, Tan X, Manseau EJ, Dvorak AM, Dvorak HF (2002) Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. J Exp Med 196(11):1497–1506PubMedCentralPubMed
72.
Zurück zum Zitat Wirzenius M, Tammela T, Uutela M, He Y, Odorisio T, Zambruno G, Nagy JA, Dvorak HF, Yla-Herttuala S, Shibuya M, Alitalo K (2007) Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting. J Exp Med 204(6):1431–1440. doi:10.1084/jem.20062642 PubMedCentralPubMed Wirzenius M, Tammela T, Uutela M, He Y, Odorisio T, Zambruno G, Nagy JA, Dvorak HF, Yla-Herttuala S, Shibuya M, Alitalo K (2007) Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting. J Exp Med 204(6):1431–1440. doi:10.​1084/​jem.​20062642 PubMedCentralPubMed
73.
Zurück zum Zitat Enholm B, Karpanen T, Jeltsch M, Kubo H, Stenback F, Prevo R, Jackson DG, Yla-Herttuala S, Alitalo K (2001) Adenoviral expression of vascular endothelial growth factor-C induces lymphangiogenesis in the skin. Circ Res 88(6):623–629PubMed Enholm B, Karpanen T, Jeltsch M, Kubo H, Stenback F, Prevo R, Jackson DG, Yla-Herttuala S, Alitalo K (2001) Adenoviral expression of vascular endothelial growth factor-C induces lymphangiogenesis in the skin. Circ Res 88(6):623–629PubMed
75.
Zurück zum Zitat Zampell JC, Avraham T, Yoder N, Fort N, Yan A, Weitman ES, Mehrara BJ (2012) Lymphatic function is regulated by a coordinated expression of lymphangiogenic and anti-lymphangiogenic cytokines. Am J Physiol Cell Physiol 302(2):C392–C404. doi:10.1152/ajpcell.00306.2011 PubMedCentralPubMed Zampell JC, Avraham T, Yoder N, Fort N, Yan A, Weitman ES, Mehrara BJ (2012) Lymphatic function is regulated by a coordinated expression of lymphangiogenic and anti-lymphangiogenic cytokines. Am J Physiol Cell Physiol 302(2):C392–C404. doi:10.​1152/​ajpcell.​00306.​2011 PubMedCentralPubMed
77.
Zurück zum Zitat Tomura M, Honda T, Tanizaki H, Otsuka A, Egawa G, Tokura Y, Waldmann H, Hori S, Cyster JG, Watanabe T, Miyachi Y, Kanagawa O, Kabashima K (2010) Activated regulatory T cells are the major T cell type emigrating from the skin during a cutaneous immune response in mice. J Clin Invest 120(3):883–893. doi:10.1172/JCI40926 PubMedCentralPubMed Tomura M, Honda T, Tanizaki H, Otsuka A, Egawa G, Tokura Y, Waldmann H, Hori S, Cyster JG, Watanabe T, Miyachi Y, Kanagawa O, Kabashima K (2010) Activated regulatory T cells are the major T cell type emigrating from the skin during a cutaneous immune response in mice. J Clin Invest 120(3):883–893. doi:10.​1172/​JCI40926 PubMedCentralPubMed
78.
Zurück zum Zitat Bellingan GJ, Caldwell H, Howie SE, Dransfield I, Haslett C (1996) In vivo fate of the inflammatory macrophage during the resolution of inflammation: inflammatory macrophages do not die locally, but emigrate to the draining lymph nodes. J Immunol 157(6):2577–2585PubMed Bellingan GJ, Caldwell H, Howie SE, Dransfield I, Haslett C (1996) In vivo fate of the inflammatory macrophage during the resolution of inflammation: inflammatory macrophages do not die locally, but emigrate to the draining lymph nodes. J Immunol 157(6):2577–2585PubMed
81.
Zurück zum Zitat Cliff S, Bedlow AJ, Stanton AW, Mortimer PS (1999) An in vivo study of the microlymphatics in psoriasis using fluorescence microlymphography. Br J Dermatol 140(1):61–66PubMed Cliff S, Bedlow AJ, Stanton AW, Mortimer PS (1999) An in vivo study of the microlymphatics in psoriasis using fluorescence microlymphography. Br J Dermatol 140(1):61–66PubMed
82.
Zurück zum Zitat Ryan TJ (1980) Microcirculation in psoriasis: blood vessels, lymphatics and tissue fluid. Pharmacol Ther 10(1):27–64PubMed Ryan TJ (1980) Microcirculation in psoriasis: blood vessels, lymphatics and tissue fluid. Pharmacol Ther 10(1):27–64PubMed
83.
Zurück zum Zitat Kovi J, Duong HD, Hoang CT (1981) Ultrastructure of intestinal lymphatics in Crohn’s disease. Am J Clin Pathol 76(4):385–394PubMed Kovi J, Duong HD, Hoang CT (1981) Ultrastructure of intestinal lymphatics in Crohn’s disease. Am J Clin Pathol 76(4):385–394PubMed
85.
Zurück zum Zitat Liao S, Ruddle NH (2006) Synchrony of high endothelial venules and lymphatic vessels revealed by immunization. J Immunol 177(5):3369–3379PubMed Liao S, Ruddle NH (2006) Synchrony of high endothelial venules and lymphatic vessels revealed by immunization. J Immunol 177(5):3369–3379PubMed
88.
Zurück zum Zitat Shi VY, Bao L, Chan LS (2012) Inflammation-driven dermal lymphangiogenesis in atopic dermatitis is associated with CD11b+ macrophage recruitment and VEGF-C up-regulation in the IL-4-transgenic mouse model. Microcirculation 19(7):567–579. doi:10.1111/j.1549-8719.2012.00189.x PubMed Shi VY, Bao L, Chan LS (2012) Inflammation-driven dermal lymphangiogenesis in atopic dermatitis is associated with CD11b+ macrophage recruitment and VEGF-C up-regulation in the IL-4-transgenic mouse model. Microcirculation 19(7):567–579. doi:10.​1111/​j.​1549-8719.​2012.​00189.​x PubMed
90.
Zurück zum Zitat Kajiya K, Sawane M, Huggenberger R, Detmar M (2009) Activation of the VEGFR-3 pathway by VEGF-C attenuates UVB-induced edema formation and skin inflammation by promoting lymphangiogenesis. J Invest Dermatol 129(5):1292–1298. doi:10.1038/jid.2008.351 PubMed Kajiya K, Sawane M, Huggenberger R, Detmar M (2009) Activation of the VEGFR-3 pathway by VEGF-C attenuates UVB-induced edema formation and skin inflammation by promoting lymphangiogenesis. J Invest Dermatol 129(5):1292–1298. doi:10.​1038/​jid.​2008.​351 PubMed
91.
Zurück zum Zitat Zhou Q, Guo R, Wood R, Boyce BF, Liang Q, Wang YJ, Schwarz EM, Xing L (2011) Vascular endothelial growth factor C attenuates joint damage in chronic inflammatory arthritis by accelerating local lymphatic drainage in mice. Arthritis Rheum 63(8):2318–2328. doi:10.1002/art.30421 PubMedCentralPubMed Zhou Q, Guo R, Wood R, Boyce BF, Liang Q, Wang YJ, Schwarz EM, Xing L (2011) Vascular endothelial growth factor C attenuates joint damage in chronic inflammatory arthritis by accelerating local lymphatic drainage in mice. Arthritis Rheum 63(8):2318–2328. doi:10.​1002/​art.​30421 PubMedCentralPubMed
92.
Zurück zum Zitat Kajiya K, Huggenberger R, Drinnenberg I, Ma B, Detmar M (2008) Nitric oxide mediates lymphatic vessel activation via soluble guanylate cyclase alpha1beta1-impact on inflammation. FASEB J 22(2):530–537. doi:10.1096/fj.07-8873com PubMed Kajiya K, Huggenberger R, Drinnenberg I, Ma B, Detmar M (2008) Nitric oxide mediates lymphatic vessel activation via soluble guanylate cyclase alpha1beta1-impact on inflammation. FASEB J 22(2):530–537. doi:10.​1096/​fj.​07-8873com PubMed
97.
Zurück zum Zitat Liao S, Cheng G, Conner DA, Huang Y, Kucherlapati RS, Munn LL, Ruddle NH, Jain RK, Fukumura D, Padera TP (2011) Impaired lymphatic contraction associated with immunosuppression. Proc Natl Acad Sci USA 108(46):18784–18789. doi:10.1073/pnas.1116152108 PubMedCentralPubMed Liao S, Cheng G, Conner DA, Huang Y, Kucherlapati RS, Munn LL, Ruddle NH, Jain RK, Fukumura D, Padera TP (2011) Impaired lymphatic contraction associated with immunosuppression. Proc Natl Acad Sci USA 108(46):18784–18789. doi:10.​1073/​pnas.​1116152108 PubMedCentralPubMed
98.
Zurück zum Zitat Breslin JW, Gaudreault N, Watson KD, Reynoso R, Yuan SY, Wu MH (2007) Vascular endothelial growth factor-C stimulates the lymphatic pump by a VEGF receptor-3-dependent mechanism. Am J Physiol Heart Circ Physiol 293(1):H709–H718. doi:10.1152/ajpheart.00102.2007 PubMed Breslin JW, Gaudreault N, Watson KD, Reynoso R, Yuan SY, Wu MH (2007) Vascular endothelial growth factor-C stimulates the lymphatic pump by a VEGF receptor-3-dependent mechanism. Am J Physiol Heart Circ Physiol 293(1):H709–H718. doi:10.​1152/​ajpheart.​00102.​2007 PubMed
99.
Zurück zum Zitat McKimmie CS, Singh MD, Hewit K, Lopez-Franco O, Le Brocq M, Rose-John S, Lee KM, Baker AH, Wheat R, Blackbourn DJ, Nibbs RJ, Graham GJ (2013) An analysis of the function and expression of D6 on lymphatic endothelial cells. Blood. doi:10.1182/blood-2012-04-425314 PubMed McKimmie CS, Singh MD, Hewit K, Lopez-Franco O, Le Brocq M, Rose-John S, Lee KM, Baker AH, Wheat R, Blackbourn DJ, Nibbs RJ, Graham GJ (2013) An analysis of the function and expression of D6 on lymphatic endothelial cells. Blood. doi:10.​1182/​blood-2012-04-425314 PubMed
100.
Zurück zum Zitat Lee KM, McKimmie CS, Gilchrist DS, Pallas KJ, Nibbs RJ, Garside P, McDonald V, Jenkins C, Ransohoff R, Liu L, Milling S, Cerovic V, Graham GJ (2011) D6 facilitates cellular migration and fluid flow to lymph nodes by suppressing lymphatic congestion. Blood 118(23):6220–6229. doi:10.1182/blood-2011-03-344044 PubMedCentralPubMed Lee KM, McKimmie CS, Gilchrist DS, Pallas KJ, Nibbs RJ, Garside P, McDonald V, Jenkins C, Ransohoff R, Liu L, Milling S, Cerovic V, Graham GJ (2011) D6 facilitates cellular migration and fluid flow to lymph nodes by suppressing lymphatic congestion. Blood 118(23):6220–6229. doi:10.​1182/​blood-2011-03-344044 PubMedCentralPubMed
101.
Zurück zum Zitat Jamieson T, Cook DN, Nibbs RJ, Rot A, Nixon C, McLean P, Alcami A, Lira SA, Wiekowski M, Graham GJ (2005) The chemokine receptor D6 limits the inflammatory response in vivo. Nat Immunol 6(4):403–411. doi:10.1038/ni1182 PubMed Jamieson T, Cook DN, Nibbs RJ, Rot A, Nixon C, McLean P, Alcami A, Lira SA, Wiekowski M, Graham GJ (2005) The chemokine receptor D6 limits the inflammatory response in vivo. Nat Immunol 6(4):403–411. doi:10.​1038/​ni1182 PubMed
102.
Zurück zum Zitat Neusser MA, Kraus AK, Regele H, Cohen CD, Fehr T, Kerjaschki D, Wuthrich RP, Penfold ME, Schall T, Segerer S (2010) The chemokine receptor CXCR7 is expressed on lymphatic endothelial cells during renal allograft rejection. Kidney Int 77(9):801–808. doi:10.1038/ki.2010.6 PubMed Neusser MA, Kraus AK, Regele H, Cohen CD, Fehr T, Kerjaschki D, Wuthrich RP, Penfold ME, Schall T, Segerer S (2010) The chemokine receptor CXCR7 is expressed on lymphatic endothelial cells during renal allograft rejection. Kidney Int 77(9):801–808. doi:10.​1038/​ki.​2010.​6 PubMed
103.
Zurück zum Zitat Ohtani O, Ohtani Y (2008) Organization and developmental aspects of lymphatic vessels. Arch Histol Cytol 71(1):1–22PubMed Ohtani O, Ohtani Y (2008) Organization and developmental aspects of lymphatic vessels. Arch Histol Cytol 71(1):1–22PubMed
104.
Zurück zum Zitat Norrmen C, Vandevelde W, Ny A, Saharinen P, Gentile M, Haraldsen G, Puolakkainen P, Lukanidin E, Dewerchin M, Alitalo K, Petrova TV (2010) Liprin (beta)1 is highly expressed in lymphatic vasculature and is important for lymphatic vessel integrity. Blood 115(4):906–909. doi:10.1182/blood-2009-03-212274 PubMedCentralPubMed Norrmen C, Vandevelde W, Ny A, Saharinen P, Gentile M, Haraldsen G, Puolakkainen P, Lukanidin E, Dewerchin M, Alitalo K, Petrova TV (2010) Liprin (beta)1 is highly expressed in lymphatic vasculature and is important for lymphatic vessel integrity. Blood 115(4):906–909. doi:10.​1182/​blood-2009-03-212274 PubMedCentralPubMed
105.
Zurück zum Zitat Halin C, Fahrngruber H, Meingassner JG, Bold G, Littlewood-Evans A, Stuetz A, Detmar M (2008) Inhibition of chronic and acute skin inflammation by treatment with a vascular endothelial growth factor receptor tyrosine kinase inhibitor. Am J Pathol 173(1):265–277. doi:10.2353/ajpath.2008.071074 PubMedCentralPubMed Halin C, Fahrngruber H, Meingassner JG, Bold G, Littlewood-Evans A, Stuetz A, Detmar M (2008) Inhibition of chronic and acute skin inflammation by treatment with a vascular endothelial growth factor receptor tyrosine kinase inhibitor. Am J Pathol 173(1):265–277. doi:10.​2353/​ajpath.​2008.​071074 PubMedCentralPubMed
108.
Zurück zum Zitat Saito Y, Nakagami H, Morishita R, Takami Y, Kikuchi Y, Hayashi H, Nishikawa T, Tamai K, Azuma N, Sasajima T, Kaneda Y (2006) Transfection of human hepatocyte growth factor gene ameliorates secondary lymphedema via promotion of lymphangiogenesis. Circulation 114(11):1177–1184. doi:10.1161/CIRCULATIONAHA.105.602953 PubMed Saito Y, Nakagami H, Morishita R, Takami Y, Kikuchi Y, Hayashi H, Nishikawa T, Tamai K, Azuma N, Sasajima T, Kaneda Y (2006) Transfection of human hepatocyte growth factor gene ameliorates secondary lymphedema via promotion of lymphangiogenesis. Circulation 114(11):1177–1184. doi:10.​1161/​CIRCULATIONAHA.​105.​602953 PubMed
Metadaten
Titel
The inflammatory response of lymphatic endothelium
verfasst von
David Aebischer
Maria Iolyeva
Cornelia Halin
Publikationsdatum
01.04.2014
Verlag
Springer Netherlands
Erschienen in
Angiogenesis / Ausgabe 2/2014
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-013-9404-3

Weitere Artikel der Ausgabe 2/2014

Angiogenesis 2/2014 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

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.

Zeitschrift für Allgemeinmedizin, DEGAM

Typ-2-Diabetes und Depression folgen oft aufeinander

14.05.2024 Typ-2-Diabetes Nachrichten

Menschen mit Typ-2-Diabetes sind überdurchschnittlich gefährdet, in den nächsten Jahren auch noch eine Depression zu entwickeln – und umgekehrt. Besonders ausgeprägt ist die Wechselbeziehung laut GKV-Daten bei jüngeren Erwachsenen.

Update Innere Medizin

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