Some Relationships among Hemostasis, Fibrinolytic Phenomena, Immunity, and the Inflammatory Response

Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation

“…112 Oscar Ratnoff, the late discoverer of factor XII, proposed the concept that blood coagulation, fibrinolysis, and inflammation are intimately related via surface contact, which he called "a seamless web of host defense reactions." 113 Together, the studies reviewed herein provide evidence that polyP is a key player in the web of host-pathogen interactions. Indeed, long-chain microbial polyP is a potent activator of the blood clotting system via the contact pathway and can trigger both thrombosis and inflammation (the latter via bradykinin generation and possibly complement activation).…”

Studies on Cystic Fibrosis Using Isoelectric Focusing. II. Demonstration of Deficient Proteolytic Cleavage of α2-Macroglobulin in Cystic Fibrosis Plasma

“…If a defect in a 2 M is responsible indirectly for the pathophysiology of CF, then the etiology of the disease would be roughly analogous to that of heredity angioneurotic edema, in that a deficiency in C1 esterase inhibitor has been found to be indirectly responsible for the pathophysiology of that disease (41). A concomitant decrease in total arginine esterase activity o r kallikrein activity in C F might be explained by assuming ( I ) hyperconversion of prekallikrein to kallikrein, brought about by plasmin (40). with subsequent inhibition of kallikrein by a , antitrypsin or C1 esterase inhibitor (24,40); (2) feedback inhibition of Hageman factor activation by uninhibited plasmin; or (3) a concurrent defect in kallikrein.…”

“…inflammatory. and complement pathways where a 2 M has been shown to interact and possibly function as a regulatory agent (24,40,41). The double-headed arrows leading to and from a 2 M indicate the points of interaction of a l M with these systems.…”

“…ellagic acid. or kaolin (40). the plasma proteases (esterases) are in an inactive or proenzyme form (21, 24.…”

“…A concomitant decrease in total arginine esterase activity o r kallikrein activity in C F might be explained by assuming ( I ) hyperconversion of prekallikrein to kallikrein, brought about by plasmin (40). with subsequent inhibition of kallikrein by a , antitrypsin or C1 esterase inhibitor (24,40); (2) feedback inhibition of Hageman factor activation by uninhibited plasmin; or (3) a concurrent defect in kallikrein. or another protease, but not plasmin.…”