Platelet Munc13-4 regulates hemostasis, thrombosis and airway inflammation.

Platelet Munc13-4 regulates hemostasis, thrombosis and airway inflammation. Haematologica. 2018 Apr 19;: Authors: Cardenas EI, Breaux K, Da Q, Flores JR, Ramos MA, Tuvim MJ, Burns AR, Rumbaut RE, Adachi R Abstract Platelet degranulation is crucial for hemostasis and may participate in inflammation. Exocytosis in platelets is mediated by SNARE proteins and should be controlled by Munc13 proteins. We found that platelets express Munc13-2 and -4. We assessed platelet granule exocytosis in Munc13-2 and -4 global and conditional KO mice, and observed that deletion of Munc13-4 ablates dense granule release and indirectly impairs alpha granule exocytosis. We found no exocytic role for Munc13-2 in platelets, not even in the absence of Munc13-4. In vitro, Munc13-4-deficient platelets exhibited defective aggregation at low doses of collagen. In a flow chamber assay, we observed that Munc13-4 acted as a rate-limiting factor in the formation of thrombi. In vivo, we observed a dose-dependency between Munc13-4 expression in platelets and both venous bleeding time and time to arterial thrombosis. Finally, in a model of allergic airway inflammation, we found that platelet-specific Munc13-4 KO mice had a reduction in airway hyperresponsiveness and eosinophilic inflammation. Taken together, our results indicate that Munc13-4-dependent platelet dense granule release plays essential roles in hemostasis, thrombosis and allergic inflammation. PMID...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research