血管生成
整合素
碱性成纤维细胞生长因子
内皮干细胞
肿瘤坏死因子α
细胞生物学
体内
生物
细胞粘附分子
受体
成纤维细胞生长因子
分子生物学
化学
癌症研究
体外
免疫学
生长因子
生物化学
生物技术
作者
Peter Vanderslice,Christy L. Munsch,Eugene Rachal,David Erichsen,Kay M. Sughrue,Ann N. Truong,James N. Wygant,Bradley W. McIntyre,Suzanne G. Eskin,Ronald G. Tilton,Peter J. Polverini
出处
期刊:Angiogenesis
[Springer Nature]
日期:1998-01-01
卷期号:2 (3): 265-275
被引量:35
标识
DOI:10.1023/a:1009296700991
摘要
Tumor necrosis factor-alpha (TNF-alpha) and fibroblast growth factor-2 (FGF-2 or bFGF) are potent stimulators of angiogenesis. TNF- alpha, but not FGF-2, can induce the expression of vascular cell adhesion molecule-1 (VCAM-1) on the surface of endothelial cells. The soluble form of VCAM-1 has recently been demonstrated to function as an angiogenic mediator. Here we demonstrate that monoclonal antibodies directed against VCAM-1 or its alpha4 integrin counter- receptor inhibited TNF-alpha-induced endothelial cell migration in vitro. Angiogenesis induced in vivo in rat corneas by TNF-alpha was inhibited by a neutralizing antibody directed against the rat alpha4 integrin subunit. A peptide antagonist of the a4 integrins blocked TNF-alpha-induced endothelial cell migration in vitro and angiogenesis in rat corneas in vivo. No inhibition by the antibodies or peptide antagonist was observed either in vitro or in vivo when FGF-2 was used as the stimulus. The peptide antagonist did not inhibit TNF-a binding to its receptor nor did it block the function of alphavbeta3, an integrin previously implicated in TNF-a and FGF- 2 mediated angiogenesis. These results demonstrate that angiogenic processes induced by TNF-alpha are mediated in part by agr;4 integrins possibly by a mechanism involving the induction of soluble VCAM-1.
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