Fibrinogen C-terminal peptidic sequences (Haptides) modulate fibrin polymerization

Gerard Marx*, Matti Ben-Moshe, Sholomo Magdassi, Raphael Gorodetsky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

We previously described synthetic peptides of 19-21 amino acid residues, homologous to the C-termini of fibrinogen Fib340 and Fib420, from the β-chain (Cβ), the extended αE chain (CαE) and near the end of the γ-chain (preCγ) which elicited attachment (haptotactic) responses from mesenchymal cells. We named these haptotactic peptides -Haptides. The effects of Haptides on fibrin clot formation was evaluated and their possible effects on platelet aggregation was examined. The Haptides Cβ, CαE and preCγ, (2-10 μM) increased fibrin clot turbidity and also decreased thrombin-induced clotting time. Higher concentrations (>120 μM of Cβ or preCγ) induced fibrinogen precipitation even without thrombin. These precipitates exhibited different ultrastructure from thrombin-induced fibrin by scanning and transmission microscopy. C-terminal peptides of the other fibrinogen chains exerted no such effects. Sepharose beads covalently coated with either whole fibrinogen or Haptides (SB-Fib or SB-Haptide) highly adsorbed free FITCHaptides. In aqueous solution, Haptides formed nano-particles with average size of ∼ 150nm in diameter. We suggest that such positively charged aggregates could serve to nucleate and accelerate fibrin gel formation. These results also indicate that Cβ and preCγ sequences within fibrin(ogen) participate in the docking and condensation of fibrin(ogen) during its assembly into a fibrin clot. By contrast, Haptides up to 1OOμM did not bind to platelets, and had no effect on platelet aggregation. Our findings highlight the roles of the C-terminal sequences of the β and γ chains in fibrin(ogen) polymerization as well as in cell attachment.

Original languageAmerican English
Pages (from-to)43-51
Number of pages9
JournalThrombosis and Haemostasis
Volume91
Issue number1
DOIs
StatePublished - Jan 2004

Keywords

  • Aggregate
  • Coagulation
  • Fibrinogen
  • Haptides
  • Turbidity

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