The autoactivation of rabbit Hageman factor.
Proteolytic cleavage and activation of isolated, single chain, zymogen Hageman factor was observed in the presence of kaolin alone. The rate of cleavage of kaolin-bound Hageman factor was enhanced 50-fold by the presence of prekallikrein and high molecular weight kininogen. The two-chain 82,000 dalton form of activated Hageman factor (alpha-HF(a)) also cleaved kaolin- bound single-chain Hageman factor in a dose-dependent manner, yielding fragments of 28,000 and, 50,000 dahons under reducing conditions. Cleavage of kaolin-bound single-chain Hageman factor was not inhibited by preincubation with diisopropylfluorophosphate (12 mM) for 10 min, but long-term incubation of Hageman factor with diisopropylfluorophosphate (up to 48 h) resulted in inhibition of cleavage of kaolin-bound Hageman factor to an extent proportional to the inhibition of procoagulant Hageman factor activity. Hageman factor cleavage was maximal when the kaolin concentration was {approximately} 10-fold greater than the Hageman factor concentration (wt:wt), and was partially inhibited by high molecular weight kininogen. Kaolin-bound Hageman factor cleaved clotting factor XI in an amount which correlated with the extent of cleavage of the Hageman factor. These findings are compatible with the concept that single-chain Hageman factor and alpha- HF(a), are both capable of cleaving and activating kaolin-bound Hageman factor and that a close molecular association of kaolin-bound Hageman factor molecules is required for this reaction.
D000818:Animals; D001778:Blood Coagulation Disorders / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005174:Factor XII / Q000302:isolation & purification / Q000378:metabolism*; D007531:Isoflurophate / Q000378:metabolism*; D007610:Kallikreins; D007616:Kaolin / Q000378:metabolism; D007704:Kininogens / Q000378:metabolism; D011288:Prekallikrein; D011817:Rabbits; D014316:Tritium
D007704:Kininogens; D014316:Tritium; D007531:Isoflurophate; D007616:Kaolin; D005174:Factor XII; D011288:Prekallikrein; D007610:Kallikreins