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Science. 2002 Jun 7;296(5574):1880-2.

Activation of endothelial cell protease activated receptor 1 by the protein C pathway.

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  • 1Department of Immunology, C204, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.


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.

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