An ancestral serine protease coagulation cascade exerts a novel function in early immune defense
A protein and protein technology, applied in the direction of peptide/protein components, cardiovascular system diseases, non-central analgesics, etc.
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[0019] Phylogenetically conserved serine protease cascades play important roles in invertebrate and vertebrate immunity. The mammalian coagulation system dates back about 400 million years and it shares homology with ancestral serine protease cascades involved in, for example, Toll receptor signaling in insects and the release of antimicrobial peptides during hemolymph clotting. The present invention shows that induction of coagulation by bacteria leads to immobilization of microorganisms within the clot and production of antimicrobial activity. In this way, the coagulation cascade of ancestral serine proteases has a new function in early immune defense. Trapping is mediated by cross-linking bacteria with fibrin fibers through the action of Factor XIII (FXIII), an evolutionarily conserved transglutaminase. Infected FXIII - / - Mice showed signs of severe pathological inflammation, whereas treatment of wild-type animals with FXIII inhibited bacterial dissemination. Bacterial k...
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