Fibrin polymerization and release of fibrinopeptide B by thrombin

A. Hurlet-Jensen, H. Z. Cummins, H. L. Nossel, C. Y. Liu

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41 Scopus citations

Abstract

Although it is well known that thrombin releases fibrinopeptide A (FPA) more rapidly than fibrinopeptide (FPB) from fibrinogen different opinions have been expressed as to whether fibrin I (FPA release) and II (FPB release) are sequential or simultaneous. Evidence has been presented that FPB release depends on the polymerization of fibrin and the finding that the tetrapeptide gly-pro-arg-pro inhibits fibrin formation provides a new tool to investigate the effect of polymerization. The radioimmunoassay technique which permits the initial rates of the release reactions to be accurately measured at low concentrations of reactants was used to investigate FPB release. In the absence of gly-pro-arg-pro the FPB release pattern showed three phases - an initial slow and a second more rapid phase both of which were at a constant rate and a final phase with decreasing rate as the substrate concentration fell. Gly-pro-arg-pro at appropriate concentrations inhibited fibrin polymerization as indicated by optical density and light scattering techniques as well as by gel filtration on Sephadex G-200. FPA release and the initial rate of FPB release were unaffected. The second phase of rapid FPB release was abolished indicating that this increased rate is entirely dependent on the polymerization of fibrin I. Under one set of specified conditions the initial release rates of FPB by thrombin from different substrates were 15.8 pmol/min (fibrinogen), 14.0 pmol/min (fibrinogen plus gly-pro-arg-pro), 27.4 pmol/min (fibrin I monomer) and 164.4 pmol/min (fibrin I polymer). The data indicate that fibrin I and II formation are not sequential but simultaneous and that it is the more rapid formation of fibrin I which results in the appearance of a sequential reaction. It is suggested that a number of other reactions in the hemostatic system including fibrinolysis which appear to be sequential are also simultaneous.

Original languageEnglish
Pages (from-to)419-427
Number of pages9
JournalThrombosis Research
Volume27
Issue number4
DOIs
StatePublished - 15 Aug 1982
Externally publishedYes

Keywords

  • Fibrin
  • Fibrinogen
  • Fibrinopeptide B
  • Gly-pro-arg-pro

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