Cellular mechanism in thrombin mediated HMGB1 release. Effect of cluster formation of HMGB1 on the cell-surface receptors.

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HMGB1, a representative danger associated molecular patterns, DAMP is released from almost all nucleated necrotic cells and activated epithelial cells including endothelial cells. The HMGB1 released out of the cells acts on Toll Like receptors(TLR)-2,TLR-4 and receptor for advanced glycation endproducts, RAGE. If the cells were primed by preceding PAMPs, pathogen associated molecular patterns, dual signalings from PAMPs and DAMPs generate and secrete IL-1b(beta) and IL-18 resulting self-defensive inflammation and hemostatic reaction. However excessive this dual signaling often reads to systemic and/or fulminant inflammation and coagulation resulting systemic inflammatory response syndrome(SIRS) and/or disseminated intravascular coagulation(DIC). We could present that for example HMGB1 and LPS or thrombin may have a crucial role in these severe conditions. Thus the regulation and intervention of PAMPs and DAMPs are important in preventive medicine in the emergency medicines.