INFLAMMATION - THE PROTEIN-C PATHWAY

The protein C pathway serves as one of the most important negative reg ulatory mechanisms in coagulation. Unlike most pathways in coagulation , the protein C pathway can be downregulated by inflammatory mediators at the levels of protein C activation and function. Antiphospholipid antibodies can selectively block protein C function. In gram negative sepsis, protein C in humans and activated protein C (APC) in baboons a nd rodents have been shown to block the lethal response, at least in p art by blocking the DIC response and probably by modulating the cytoki ne cascade. The mechanisms by which the pathway modulates inflammation remains unclear, but a novel endothelial cell specific receptor has r ecently been identified that binds APC and modulates enzyme specificit y. Like thrombomodulin, the receptor is downregulated by the inflammat ory cytokine, TNF. These observations provide a basis for a model in w hich the protein C pathway serves as a major regulatory mechanism in t he control of coagulation and inflammation.