Busso N et al. - Soluble tissue factor (sTF) induces acute inflammation through a thrombin-dependent pathway and both fibrin deposition and platelet activation are essential steps in this process. The activation of protease activated receptor-4 (PAR-4) on platelets is crucial and the other PARs do not play a major role in sTF-induced inflammation. Methods
Mechanisms behind the TF activation of the coagulation proteases enhancing inflammation in arthritis and endotoxemia were studied
Extravascular inflammation was induced by injection of recombinant sTF1-219 in the hind paw
Effects of thrombin inhibition, fibrinogen and platelet depletion were evaluated
Effects of PAR deficiency using knockout mice deficient for each of the PARs was also investigated
Results
Injection of sTF provoked a rapid onset of paw swelling
Inflammation was confirmed histologically and by increased serum IL-6 levels
Inflammation was reduced by depletion of fibrinogen or platelets, by treatment with hirudin or an inhibitor of Factor VIIa
PAR-4 deficient mice exhibited a reduced paw swelling
In contrast, a deficiency in either PAR-1, PAR-2- or PAR-3 did not affect the inflammatory response to sTF injection
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