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Langer, H.F.* ; Chung, K.-J.* ; Orlova, V.V.* ; Choi, E.Y.* ; Kaul, S.* ; Kruhlak, M.J.* ; Alatsatianos, M.* ; de Angelis, R.A.* ; Roche, P.A.* ; Magotti, P.* ; Li, X.* ; Economopoulou, M.* ; Rafail, S.* ; Lambris, J.D.* ; Chavakis, T.*

Complement-mediated inhibition of neovascularization reveals a point of convergence between innate immunity and angiogenesis.

Blood 116, 4395-4403 (2010)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Beyond its role in immunity, complement mediates a wide range of functions in the context of morphogenetic or tissue remodeling processes. Angiogenesis is crucial during tissue remodeling in multiple pathologies; however, the knowledge about the regulation of neovascularization by the complement components is scarce. Here we studied the involvement of complement in pathological angiogenesis. Strikingly, we found that mice deficient in the central complement component C3 displayed increased neovascularization in the model of retinopathy of prematurity (ROP) and in the in vivo Matrigel plug assay. In addition, antibody-mediated blockade of C5, treatment with C5aR antagonist, or C5aR deficiency in mice resulted in enhanced pathological retina angiogenesis. While complement did not directly affect angiogenesis-related endothelial cell functions, we found that macrophages mediated the antiangiogenic activity of complement. In particular, C5a-stimulated macrophages were polarized toward an angiogenesis-inhibitory phenotype, including the up-regulated secretion of the antiangiogenic soluble vascular endothelial growth factor receptor-1. Consistently, macrophage depletion in vivo reversed the increased neovascularization associated with C3- or C5aR deficiency. Taken together, complement and in particular the C5a-C5aR axes are potent inhibitors of angiogenesis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Zeitschrift Blood
Quellenangaben Band: 116, Heft: 22, Seiten: 4395-4403 Artikelnummer: , Supplement: ,
Verlag American Society of Hematology
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)