Localization and regulation in reactive sites of DAMPs/PAMPs. Role of ATP from the activated plateles

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Dual signalings from PAMPs/DAMPs play crucial role in inflammation, immunity and hemostasis. It has been listed more than 1000 of molecules as PAMPs, and DAMPs each other.In this study, we took LPS as PAMPs,and HMGB-1 and ATP as DAMPs, and stimulated macrophages or dendritic cells. We showed that dual signaling from LPS and HMGB1 or ATP stimulated the release of IL-1b(beta) and IL-18.Thus dual signaling plays crucial role in inflammation, immunity and hemostasis. It has been described that platelet contains inflammasome, however the role of platelet-inflammasome has been not known. We examined the role of platelet inflammasome. An inflammasome inhibitor,1,5-anhydrofructose inhibited platelets aggregation with decreased release of IL-1b(beta). Thus ATP from activated platelets might play important role for the hemostasis/inflammation.