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. 2002 Jun 7;296(5574):1880-2.
doi: 10.1126/science.1071699.

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

Matthias Riewald  1 , Ramona J Petrovan, Aaron Donner, Barbara M Mueller, Wolfram Ruf
Affiliations

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

Matthias Riewald et al. Science. .

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.

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