Fibrin ε-(γ-glutamyl)lysine crosslink acceleration by red blood cells

Abstract

FIBRIN, the skeletal protein of thrombi, is derived from its soluble Pl.asma precursor, fibrinogen. Fibrinogen has a molecular weight of ∼340,000. It is composed of three pairs of subunit polypeptide chains, Aα, Bβ, and γ, of molecular weights 68,000, 56,000 and 49,000, respectively, joined by disulphide bonds. The serine protease thrombin releases fibrinopeptides A and B from the amino terminal end of the Aα- and Bβ-chains of fibrinogen to leave the α- and β-chains of fibrin monomer. Fibrin monomers then align by noncovalent interactions to give a fibrin polymer gel. Under the influence of thrombin-activated factor XIII (factor XHIa, activated fibrin stabilising factor, Plasma transglutaminase) and calcium ion, covalent ε-(γ-glu-tamyl)lysine crosslinks are rapidly formed between γ-chains of adjacent fibrin monomers to give the γ-dimer subunit of partially crosslinked fibrin¹. The γ-crosslinking transforms the clot into a covalently bonded polymer, rendering it insoluble in 3 M urea and other agents that disrupt noncovalent interactions². Extensive crosslinking of the α-chain to give the ^α-polymer subunit of fully crosslinked fibrin requires several hours in Plasma and confers relative Plasmin resistance to the clot³. We report here an increased rate and extent of α-crosslinking when red blood cells are present in the fibrin clot.