Proteolysis of human thrombin generates novel host defense peptides

The coagulation system is characterized by the sequential and highly localized activation of a series of serine proteases,culminating in the conversion of fibrinogen into fibrin,and formation of a fibrin clot. here we show that c-terminal peptides of thrombin,a key enzyme in the coagulation cascade,constitute a novel class of host defense peptides,released upon proteolysis of thrombin in vitro,and detected in human wounds in vivo. under physiological conditions,these peptides exert antimicrobial effects against gram-positive and gram-negative bacteria,mediated by membrane lysis,as well as immunomodulatory functions,by inhibiting macrophage responses to bacterial lipopolysaccharide. in mice,they are protective against p. aeruginosa sepsis,as well as lipopolysaccharide-induced shock. moreover,the thrombin-derived peptides exhibit helical structures upon binding to lipopolysaccharide and can also permeabilize liposomes,features typical of classical helical antimicrobial peptides. these findings provide a novel link between the coagulation system and hostdefense peptides,two fundamental biological systems activated in response to injury and microbial invasion. © 2010 papareddy et al.