C5a promotes migration, proliferation, and vessel formation in endothelial cells |
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Authors: | Ryuji Kurihara Kunihiro Yamaoka Norifumi Sawamukai Shohei Shimajiri Koichi Oshita Sonosuke Yukawa Mikiko Tokunaga Shigeru Iwata Kazuyoshi Saito Kenji Chiba Yoshiya Tanaka |
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Institution: | 1. The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, 807-8555, Japan 2. Department of Pathology and Cell Biology, University of Occupational and Environmental Health, Japan, Kitakyushu, 807-8555, Japan 3. Pharmacology Laboratory, Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama, 227-0033, Japan
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Abstract: | Objectives The goal of this paper is to investigate the effects of activated complement C5a on vascular endothelium during vessel formation. Methods A human microvascular endothelial cell line (HMEC-1) derived from post-capillary venules in skin was used to measure DNA synthesis, proliferation and cell-cycle progression. In vitro ring-shaped formation by the cells was assessed by using type I collagen gel matrix and a cell-migration assay using the Chemotaxicell chamber. A Matrigel plug assay was performed to confirm the effect of C5a in vivo. Results C5a progressed the cell cycle of HMEC-1 into G2/M phases, and induced DNA synthesis and proliferation in a dose-dependent manner. C5a efficiently induced migration and ring-shaped structure formation both in vitro and in vivo. Furthermore, a C5a receptor antagonist (W-54011) suppressed all HMEC-1 activities including proliferation and migration. Conclusions Proliferation, migration, and ring-shaped formation by HMEC-1 cells was induced by C5a. The actions were efficiently inhibited by a specific antagonist against C5a. Our results implicated C5a in vessel formation and as a potent target for management of inflammatory diseases. |
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