New Mechanisms for Vascular Control of Inflammation Mediated by Natural Anticoagulant Proteins

It has been appreciated for a very long time that infections, particularly bacterial infections of the blood leading to severe sepsis, trigger a hypercoaguable state that sometimes leads to overt disseminated intravascular coagulation. We now recognize that endotoxins and other bacterial, fungal, and viral products can activate the toll receptors, leading to the elaboration of inflammatory cytokines (1) that in turn elicit tissue factor expression to trigger the blood clotting process (2). More recently, we have begun to appreciate the critical role played by natural anticoagulants in controlling the processes leading to septic shock (3). Of these natural anticoagulants, the protein C anticoagulant pathway seems to play a particularly important role in dampening the inflammatory response that occurs with endotoxin and bacteremia. It has now become clear that many of the components in the pathway possess multiple activities that...