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.
Gao
Baochong
B
Department of Physiology, Albany Medical College, Albany, NY 12208, USA. baochong.gao@med.va.gov
Saba
Thomas M
TM
Tsan
Min-Fu
MF
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D022081:Cell Surface Extensions / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008856:Microscopy, Fluorescence; D011651:Pulmonary Artery; D017469:Receptors, Fibronectin / Q000037:antagonists & inhibitors / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D019138:Antibodies, Blocking; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; D014409:Tumor Necrosis Factor-alpha