Activation of Endothelial Cell Protease Activated Receptor 1 by the Protein C Pathway
Top Cited Papers
- 7 June 2002
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 296 (5574) , 1880-1882
- https://doi.org/10.1126/science.1071699
Abstract
The coagulant and inflammatory exacerbation in sepsis is counterbalanced by the protective protein C (PC) pathway. Activated PC (APC) was shown to use the endothelial cell PC receptor (EPCR) as a coreceptor for cleavage of protease activated receptor 1 (PAR1) on endothelial cells. Gene profiling demonstrated that PAR1 signaling could account for all APC-induced protective genes, including the immunomodulatory monocyte chemoattractant protein-1 (MCP-1), which was selectively induced by activation of PAR1, but not PAR2. Thus, the prototypical thrombin receptor is the target for EPCR-dependent APC signaling, suggesting a role for this receptor cascade in protection from sepsis.Keywords
This publication has 21 references indexed in Scilit:
- Glycosylation and the activation of proteinase‐activated receptor 2 (PAR2) by human mast cell tryptaseBritish Journal of Pharmacology, 2001
- Dysfunction of Endothelial Protein C Activation in Severe Meningococcal SepsisNew England Journal of Medicine, 2001
- Gene Expression Profile of Antithrombotic Protein C Defines New Mechanisms Modulating Inflammation and ApoptosisJournal of Biological Chemistry, 2001
- Identification of the Protein C/Activated Protein C Binding Sites on the Endothelial Cell Protein C ReceptorJournal of Biological Chemistry, 2001
- Novel Protective Effects of Stem Cell Factor in a Murine Model of Acute Septic Peritonitis: Dependence on MCP-1The American Journal of Pathology, 2000
- Activated protein C suppresses tissue factor expression on U937 cells in the endothelial protein C receptor-dependent mannerFEBS Letters, 2000
- Feedback Inhibition of Macrophage Tumor Necrosis Factor-α Production by TristetraprolinScience, 1998
- Antithrombotic effects of thrombin-induced activation of endogenous protein C in primates.Journal of Clinical Investigation, 1993
- Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock.Journal of Clinical Investigation, 1993
- Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon.Journal of Clinical Investigation, 1987