The anticoagulant and anti-inflammatory roles of the protein C anticoagulant pathway.

Recent research has revealed a number of links between inflammation and coagulation. The protein C anticoagulant pathway appears to be the major pathway involved in the cross-talk between inflammation and coagulation. Studies indicate that inflammatory mediators can downregulate key components of the pathway through transcriptional control, proteolytic inactivation and oxidant damage. In turn, in vivo and in vitro studies have revealed mechanisms by which the components of the pathway may inhibit inflammatory responses. These include inhibition of cytokine responses to endotoxin, inhibition of leukocyte attachment to the activated endothelium and inhibition of thrombin and factor Xa generation in the microcirculation where both enzymes can lead to endothelial cell activation, further potentiating the inflammatory response. The ability of the protein C system to modulate both inflammation and coagulation may explain i part why specific defects in the pathway appear to be associated with both arterial and venus thrombosis.