Activation of endothelial cell protease activated receptor 1 by the protein C pathway |
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Authors: | Riewald Matthias Petrovan Ramona J Donner Aaron Mueller Barbara M Ruf Wolfram |
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Institution: | Department of Immunology, C204, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. |
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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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