C5a promotes migration, proliferation, and vessel formation in endothelial cells.
OBJECTIVE
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.
Kurihara
Ryuji
R
The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
Yamaoka
Kunihiro
K
Sawamukai
Norifumi
N
Shimajiri
Shohei
S
Oshita
Koichi
K
Yukawa
Sonosuke
S
Tokunaga
Mikiko
M
Iwata
Shigeru
S
Saito
Kazuyoshi
K
Chiba
Kenji
K
Tanaka
Yoshiya
Y
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003167:Complement Activation; D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000276:immunology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D009389:Neovascularization, Pathologic
D015936:Complement C5a