We are analyzing the pathways that mediate cross-talk between coagulation and inflammation (Figure 6). Gram-negative bacterial infections can release LPS into the circulation and activate both coagulation and inflammatory pathways. LPS induction of TF expression on monocytes activates the coagulation cascade and results in thrombin formation. Thrombin serves as a mediator between coagulation and inflammation through activation of PARs. Thrombin activates PAR-1, PAR-3, and PAR-4 on a variety of cells and induces a wide array of cellular responses. Activation of PAR-2 has been shown to increase inflammation in some disease models. Inhibiton of PAR signaling may be a useful strategy to attenuate coagulation and inflammation.
Figure 6: Cross-talk between coagulation and inflammation