Thrombin-induced fibrinopeptide B release from normal and variant fibrinogens: influence of inhibitors of fibrin polymerization.
Thrombin preferentially cleaves fibrinopeptides A (FPA) from fibrinogen resulting in the formation of desAA-fibrin from which most of the fibrinopeptides B (FPB) are then released with an enhanced rate. Kinetics of fibrinopeptide release from normal and dysfunctional fibrinogens were investigated in order to further characterize the mechanism of accelerated FPB release during desAA-fibrin polymerization. Dysfunctional fibrinogens London I and Ashford, exhibiting primary polymerization abnormalities (i.e., an abnormality present when all fibrinopeptides have been cleaved), which in the case of fibrinogen London I is believed to be caused by a defect in the D-domain, were shown to exhibit a decreased rate of FPB release compared with normal fibrinogen. While Gly-Pro-Arg-Pro, an inhibitor of fibrin polymerization, was shown to decrease the rate of FPB release from normal fibrinogen by a factor of 5, normal fragment D1, although inhibiting clot formation of normal fibrinogen, did not influence the acceleration of FPB release. On the other hand, the presence of fragment D1 did not enhance FPB release from fibrinogen London I, suggesting that interaction of D-domains in functional isolation with desAA-fibrin E-domains is not sufficient to enhance FPB release. Although clot formation was inhibited by the concentrations of fragment D1 used, the formation of small desAA-fibrin oligomers was hardly affected. Thus, small fibrin polymers, but not desAA-fibrin monomers, act as optimal substrates for the release of FPB by thrombin.
Ruf
W
W
Clinical Research Unit for Blood Coagulation and Thrombosis, Max-Planck-Gesellschaft, Justus-Liebig-Universität, Giessen F.R.G.
Bender
A
A
Lane
D A
DA
Preissner
K T
KT
Selmayr
E
E
Müller-Berghaus
G
G
D001778:Blood Coagulation Disorders; D005337:Fibrin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D015241:Fibrinogens, Abnormal; D005345:Fibrinopeptide B / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009391:Nephelometry and Turbidimetry; D011108:Polymers; D013917:Thrombin / Q000378:metabolism*
D015241:Fibrinogens, Abnormal; D011108:Polymers; C055827:fibrinogen Ashford; C055826:fibrinogen London I; D005345:Fibrinopeptide B; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin