'Role Reversal' for the Receptor PAR1 in Sepsis-induced Vascular Damage

Overview

Journal Nat Immunol

Date 2007 Oct 30

PMID 17965715

Citations 115

Authors

Nicole C Kaneider

Andrew J Leger

Anika Agarwal

Nga Nguyen

George Perides

Claudia Derian

Lidija Covic

Athan Kuliopulos

Affiliations

Soon will be listed here.

Abstract

Sepsis is a deadly disease characterized by considerable derangement of the proinflammatory, anti-inflammatory and coagulation responses. Protease-activated receptor 1 (PAR1), an important regulator of endothelial barrier function and blood coagulation, has been proposed to be involved in the lethal sequelae of sepsis, but it is unknown whether activation of PAR1 is beneficial or harmful. Using a cell-penetrating peptide (pepducin) approach, we provide evidence that PAR1 switched from being a vascular-disruptive receptor to a vascular-protective receptor during the progression of sepsis in mice. Unexpectedly, we found that the protective effects of PAR1 required transactivation of PAR2 signaling pathways. Our results suggest therapeutics that selectively activate PAR1-PAR2 complexes may be beneficial in the treatment of sepsis.

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