Signaling through CD31 protects endothelial cells from apoptosis

Endothelial damage has been implicated in the pathogenesis of chronic rejection. Conversely, expression of protective genes [including A20, A1, bcl-xl, and hemoxygenase-1 (HO-1)1 in the endothelium has been associated with long-term graft survival. Overexpression of protective genes in cultured endothelial cells confers protection from apoptosis and prevents expression of inflammatory molecules through inactivation of NF-kappaB, CD31 (PECAM-1) expressed at endothelial cell. junctions is ligated by leukocytes during transendothelial migration, Our laboratory has recently shown that cross-linking CD31 using a monoclonal antibody (LCI-4) triggers signaling events in endothelial cells. In this study, we demonstrate that treatment with LCI-4 protected serum-starved endothelial cells from apoptosis, CD31 cross-linking also led to elevation of A20 and A1 mRNA levels and activation of the transcription factor Sp-1, In summary, signaling through CD31 on endothelial cells leads to protection from apoptosis in association with up-regulation of two protective molecules, A20 and A1.