title: The intrinsic coagulation-kinin pathway, complement cascades, plasma renin-angiotensin system, and their interrelationships.
abstract: Activation of the classical complement pathway is initiated by immune complexes consisting of IgM antibody or IgG subclasses 1, 2, and 3. Binding to Clq leads to activation of C1s and digestion of C4 and C2 to yield a C3 convertase. The alternative complement pathway is initiated by complex polysaccharides as well as immune complexes of the IgA class which interact with Factors B, D, C3, and properdin to yield a stabilized C3 convertase consisting of PC3Bb. Cleavage of C3 and C5 by either pathway yields the C3a and C5a anaphylatoxins which cause histamine release from mast cells and formation of the C5b6789 attack complex causes cell lysis. Both immunologic and nonimmunologic tissue damage can initiate the surface dependent pathways of coagulation, fibrinolysis, and kinin formation. Surface bound Hageman Factor interacts with complexes of prekallikrein and HMW-kininogen as well as Factor XI and HMW-kininogen to form activated Hageman factor, kallikrein, and Factor XIa. Factor XIa continues the coagulation pathway, kallikrein and Factor XIa convert plasminogen to plasmin and kallikrein digests HMW-kininogen to yield bradykinin. The Cl inhibitor, which inactivates Cls is the major plasma inhibitor of activated Hageman factor and kallikrein. In its absence, a potentially fatal form of angioedema is seen. The inactivator of the C3a and C5a anaphylatoxins is identical to carboxypeptidase N, the major plasma inactivator of bradykinin thus demonstrating the common control mechanisms which regulate the complement and kinin-forming pathways.
mesh_terms: D001777:Blood Coagulation; D001920:Bradykinin / Q000097:blood; D003167:Complement Activation; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D005172:Factor XI / Q000378:metabolism; D005174:Factor XII / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D005342:Fibrinolysis; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology; D007610:Kallikreins / Q000378:metabolism; D007705:Kinins / Q000097:blood*; D011288:Prekallikrein; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System
chemical_list: D007705:Kinins; D005174:Factor XII; D005172:Factor XI; D011288:Prekallikrein; D007610:Kallikreins; D012083:Renin; D001920:Bradykinin