Activated protein C-cleaved protease activated receptor-1 is retained on the endothelial cell surface even in the presence of thrombin.

ABSTRACT: Activated protein C (APC) signals in endothelial cells ex vivo through protease activated receptor-1 (PAR1). However, it is controversial whether PAR1 can mediate APC's protective effects in sepsis because the inflammatory response results in thrombin generation and thrombin proteolytically activates PAR1 much more efficiently than APC. Here we show that APC can induce powerful barrier protective responses in an endothelial cell monolayer in the presence of thrombin. Using cell surface immunoassays with conformation sensitive monoclonal anti-PAR1 antibodies we analyzed cleavage of endogenous PAR1 on the endothelial cell surface by APC in the absence and presence of thrombin. Incubation with APC caused efficient PAR1 cleavage and upon coincubation with thrombin APC supported additional PAR1

SUBMITTER: Schuepbach RA 

PROVIDER: S-EPMC2254534 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature