Role of v 3-integrin in TNF- -induced endothelial cell migration

Gao, Baochong, Thomas M. Saba, and Min-Fu Tsan. Role of v 3-integrin in TNF-induced endothelial cell migration. Am J Physiol Cell Physiol 283: C1196–C1205, 2002. First published June 26, 2002; 10.1152/ajpcell.00064.2002.— Tumor necrosis factor(TNF), 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 TNFcaused an increase in the formation of membrane protrusions and cell migration. Fluorescence microscopy revealed an increase in v 3 focal contacts but a decrease in 5 1 focal contacts in TNF-treated cells. In addition, both cell-surface and total cellular expression of v 3-integrins increased significantly, whereas the expression of 5 1-integrins was unaltered. Only focal contacts containing v 3but not 5 1-integrins were present in membrane protrusions of cells at the migration front. In contrast, robust focal contacts containing 5 1integrins were present in cells behind the migration front. A blocking antibody to v 3, but not a blocking antibody to 5-integrins, significantly inhibited TNF-induced cell migration. These results indicate that in response to TNF, endothelial cells may increase the activation and ligation of v 3 while decreasing the activation and ligation of 5 1integrins to facilitate cell migration, a process essential for vascular wound healing and angiogenesis.