Endothelial cell PECAM-1 confers protection against endotoxic shock. Am J Physiol Heart Circ Physiol 2005 Jan;288(1):H159-64
Date
08/21/2004Pubmed ID
15319204DOI
10.1152/ajpheart.00500.2004Scopus ID
2-s2.0-11144278572 (requires institutional sign-in at Scopus site) 96 CitationsAbstract
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.
Author List
Maas M, Stapleton M, Bergom C, Mattson DL, Newman DK, Newman PJAuthors
Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of WisconsinDebra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCapillary Permeability
Cytoprotection
Disease Susceptibility
Endothelial Cells
Inflammation
Mice
Mice, Knockout
Platelet Endothelial Cell Adhesion Molecule-1
Shock, Septic