Angiogenesis induced by tumor necrosis factor-α is mediated by α4 integrins

被引：36

作者：

Vanderslice P. ^{[1
,6
]}

Munsch C.L. ^{[2
]}

Rachal E. ^{[1
]}

Erichsen D. ^{[3
]}

Sughrue K.M. ^{[3
]}

Truong A.N. ^{[1
]}

Wygant J.N. ^{[4
]}

McIntyre B.W. ^{[4
]}

Eskin S.G. ^{[2
]}

Tilton R.G. ^{[2
]}

Polverini P.J. ^{[5
]}

机构：

[1] Department of Immunology, Texas Biotechnology Corporation, Houston, TX

[2] Department of Cell Biology, Texas Biotechnology Corporation, Houston, TX

[3] Department of Pharmacology, Texas Biotechnology Corporation, Houston, TX

[4] Department of Immunology, Univ. Texas M.D. Anderson Cancer C., Houston, TX

[5] Dept. Oral Med., Pathol. and Surg., University of Michigan, Ann Arbor, MI

[6] Texas Biotechnology Corporation, Houston, TX 77030

来源：

Angiogenesis | 1998年 / 2卷 / 3期

关键词：

Integrin; Human Umbilical Vein Endothelial Cell; Endothelial Cell Migration; Urokinase Receptor; Peptide Antagonist;

D O I：

10.1023/A:1009296700991

中图分类号：

学科分类号：

摘要：

Tumor necrosis factor-α (TNF-α) and fibroblast growth factor-2 (FGF-2 or bFGF) are potent stimulators of angiogenesis. TNF-α, 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 α4 integrin counter-receptor inhibited TNF-α-induced endothelial cell migration in vitro. Angiogenesis induced in vivo in rat corneas by TNF-α was inhibited by a neutralizing antibody directed against the rat α4 integrin subunit. A peptide antagonist of the α4 integrins blocked TNF-α-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-α binding to its receptor nor did it block the function of αvβ3, an integrin previously implicated in TNF-α and FGF-2 mediated angiogenesis. These results demonstrate that angiogenic processes induced by TNF-α are mediated in part by α4 integrins possibly by a mechanism involving the induction of soluble VCAM-1.

引用

页码：265 / 275

页数：10

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