Signaling through CD31 protects endothelial cells from apoptosis

Endothelial damage has been implicated in the pathogenesis of chronic rejec tion. Conversely, expression of protective genes [including A20, A1, bcl-xl , and hemoxygenase-1 (HO-1)1 in the endothelium has been associated with lo ng-term graft survival. Overexpression of protective genes in cultured endo thelial cells confers protection from apoptosis and prevents expression of inflammatory molecules through inactivation of NF-kappaB, CD31 (PECAM-1) ex pressed at endothelial cell. junctions is ligated by leukocytes during tran sendothelial migration, Our laboratory has recently shown that cross-linkin g CD31 using a monoclonal antibody (LCI-4) triggers signaling events in end othelial cells. In this study, we demonstrate that treatment with LCI-4 pro tected serum-starved endothelial cells from apoptosis, CD31 cross-linking a lso led to elevation of A20 and A1 mRNA levels and activation of the transc ription factor Sp-1, In summary, signaling through CD31 on endothelial cell s leads to protection from apoptosis in association with up-regulation of t wo protective molecules, A20 and A1.