Tumor necrosis factor alpha-induced vascular leakage involves PECAM1 phosphorylation

E Ferrero, A Villa, M E Ferrero, E Toninelli, J R Bender, R Pardi, M R Zocchi
1996 Cancer Research  
Herein we show that exposure of human umbilical vein endothelial cells to tumor necrosis factor alpha (TNFalpha) led to platelet endothelial cell adhesion molecule-1 (PECAM1) surface redistribution, disruption of cytoskeleton connections, and increased PECAM1 phosphorylation, accompanied by increased permeability to macromolecules. The in vitro use of inhibitors of tyrosine or serine-threonine kinases could prevent both PECAM1 surface redistribution and the increase in permeability induced by
more » ... e cytokine. In vivo administration of lavendustin A, a natural tyrosine kinase inhibitor, protected endothelial cells from TNFalpha-dependent vascular leakage in mouse liver. We propose that the involvement of PECAM1 in TNFalpha-mediated effects on vascular permeability may depend on a dynamically regulated cytoskeletal association, related to the degree of PECAM1 phosphorylation.
pmid:8764109 fatcat:n4rnno3nbnblzmijfgjbvziy44