Role of alpha(v)beta(3)-integrin in TNF-alpha-induced endothelial cell migration.

Tumor necrosis factor-alpha (TNF-alpha), one of the major inflammatory cytokines, is known to influence endothelial cell migration. In this study, we demonstrate that exposure of calf pulmonary artery endothelial cells to TNF-alpha caused an increase in the formation of membrane protrusions and cell migration. Fluorescence microscopy revealed an increase in alpha(v)beta(3) focal contacts but a decrease in alpha(5)beta(1) focal contacts in TNF-alpha-treated cells. In addition, both cell-surface and total cellular expression of alpha(v)beta(3)-integrins increased significantly, whereas the expression of alpha(5)beta(1)-integrins was unaltered. Only focal contacts containing alpha(v)beta(3)- but not alpha(5)beta(1)-integrins were present in membrane protrusions of cells at the migration front. In contrast, robust focal contacts containing alpha(5)beta(1)-integrins were present in cells behind the migration front. A blocking antibody to alpha(v)beta(3), but not a blocking antibody to alpha(5)-integrins, significantly inhibited TNF-alpha-induced cell migration. These results indicate that in response to TNF-alpha, endothelial cells may increase the activation and ligation of alpha(v)beta(3) while decreasing the activation and ligation of alpha(5)beta(1)-integrins to facilitate cell migration, a process essential for vascular wound healing and angiogenesis.