Fibrinogen C-terminal peptidic sequences (Haptides) modulate fibrin polymerization.
We previously described synthetic peptides of 19-21 amino acid residues, homologous to the C-termini of fibrinogen Fib(340) and Fib(420), from the beta-chain (Cbeta), the extended alphaE chain (CalphaE) and near the end of the gamma-chain (preCgamma) 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 Cbeta,CalphaE and preCgamma, (2-10 micro M) increased fibrin clot turbidity and also decreased thrombin-induced clotting time. Higher concentrations (>120 micro M of Cbeta or preCgamma) induced fibrinogen precipitation even without thrombin. These precipi-tates 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 (FITC) Haptides. In aqueous solution, Haptides formed nano-par-ticles with average size of approximately 150 nm in diameter. We suggest that such positively charged aggregates could serve to nucleate and accelerate fibrin gel formation. These results also indicate that Cbeta and preCgamma 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 100 micro M did not bind to platelets, and had no effect on platelet aggregation. Our findings highlight the roles of the C-terminal sequences of the beta and gamma chains in fibrin(ogen) polymerization as well as in cell attachment.
Marx
Gerard
G
HAPTO Biotech (Israel) Ltd. PO Box 12275, Jerusalem 91121, Israel 91121. gmarx@hapto.co.il
Ben-Moshe
Matti
M
Magdassi
Sholomo
S
Gorodetsky
Raphael
R
D001777:Blood Coagulation; D001792:Blood Platelets / Q000737:chemistry; D005337:Fibrin / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D010455:Peptides / Q000737:chemistry*; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013500:Surface Tension; D013917:Thrombin / Q000737:chemistry; D013997:Time Factors; D014945:Wound Healing
D008024:Ligands; D010455:Peptides; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin