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)] 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.
Molecular Immunology Programme, The Babraham Institute, Cambridge, UK.
P C
PC
Evans
E R
ER
Taylor
P J
PJ
Kilshaw
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D015533:Transcriptional Activation
D019408:Platelet Endothelial Cell Adhesion Molecule-1