title: High affinity binding of factor XIIa to an electronegative surface controls the rates of factor XII and prekallikrein activation in vitro.
abstract: The incubation of normal human plasma in the presence of sulphatide vesicles results in the generation of amidolytic activity due to factor XIIa (FXIIa) and to kallikrein (KRN). The progress of the generation of the enzymes distinguished a high initial rate of enzyme generation, a decline of this rate to maximum amidolytic activity ([FXIIa]m and [KRN]m) and a negative pseudo-first-order rate attributed to enzyme inactivation by plasma C1-inhibitor (C1INH). [FXIIa]m and [KRN]m were determined after the treatment of various dilutions of plasma in the presence of 4, 15, or 40 microM sulphatide vesicles. At all levels of sulphatides, [FXIIa]m and [KRN]m initially increased with the concentration of plasma, to reach a plateau at higher concentration of plasma. The plateau activities of the generated enzymes and the optimal concentration of plasma both increased with the level of sulphatide vesicles. The pseudo-first-order inactivation rate for KRN increased progressively with the concentration of plasma but the respective rate for FXIIa was independent of the plasma concentration. The data suggest that contiguous binding of plasma FXIIa, factor XII (FXII), and the complexes of high molecular weight kininogen (HK) with prekallikrein (HK-PKRN) and factor XI (HK-FXI) to an electronegative surface induces a rapid generation of FXIIa and KRN. The concentration of the electronegative surface controls the levels of generated FXIIa and KRN and their release to the bulk phase. The released FXIIa and KRN are both inactivated by C1INH.
authors.affiliation: MRC Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, St. Bartholomew's and the Royal London School of Medicine and Dentistry, University of London, United Kingdom.
authors.forename: K A
authors.initials: KA
authors.lastname: Mitropoulos
mesh_terms: D000201:Activation Analysis; D000818:Animals; D002417:Cattle; D002554:Cerebrosides / Q000494:pharmacology*; D005174:Factor XII / Q000378:metabolism*; D006801:Humans; D016234:Kallikrein-Kinin System; D007704:Kininogens / Q000378:metabolism; D010949:Plasma / Q000378:metabolism*; D011288:Prekallikrein / Q000378:metabolism*; D012044:Regression Analysis
chemical_list: D002554:Cerebrosides; D007704:Kininogens; C083015:cerebroside sulfate; D005174:Factor XII; D011288:Prekallikrein