Endothelial cell PECAM-1 confers protection against endotoxic shock.
Platelet endothelial cell adhesion molecule-1 (PECAM-1; CD31) is a 130-kDa member of the Ig superfamily that is expressed on platelets and leukocytes and is highly enriched at endothelial cell-cell junctions. Previous studies showed that this vascular cell adhesion and signaling receptor functions to regulate platelet activation and thrombosis, to suppress apoptotic cell death, to mediate transendothelial migration of leukocytes, and to maintain the integrity of the vasculature. Because systemic exposure to the bacterial endotoxin LPS triggers an acute inflammatory response that involves many of these same processes, we compared the pathophysiological responses of wild-type versus PECAM-1-deficient mice to LPS challenge. We found that PECAM-1-deficient mice were significantly more sensitive to systemic LPS administration than their wild-type counterparts and that the lack of PECAM-1 expression at endothelial cell-cell junctions could account for the majority of the increased LPS-induced mortality observed. The diverse functional roles played by PECAM-1 in thrombosis, inflammation, apoptosis, and the immune response may make this molecule an attractive target for the development of novel therapeutics to manage and treat endotoxic shock.
Maas
Matthias
M
Blood Research Institute, Blood Center of Southeastern Wisconsin, PO Box 2178, 638 N. 18th St., Milwaukee, WI 53201, USA.
Stapleton
Michelle
M
Bergom
Carmen
C
Mattson
David L
DL
Newman
Debra K
DK
Newman
Peter J
PJ
D000818:Animals; D002199:Capillary Permeability; D019610:Cytoprotection; D004198:Disease Susceptibility; D042783:Endothelial Cells / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced; D051379:Mice; D018345:Mice, Knockout; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D012772:Shock, Septic / Q000503:physiopathology*
D019408:Platelet Endothelial Cell Adhesion Molecule-1