Activation of Endothelial Cell Protease Activated Receptor 1 by the Protein C Pathway
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.
- Publication:
-
Science
- Pub Date:
- June 2002
- DOI:
- 10.1126/science.1071699
- Bibcode:
- 2002Sci...296.1880R
- Keywords:
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- CELL BIOL