STUDIES ON THE ULTRASTRUCTURE OF FIBRIN LACKING FIBRINOPEPTIDE B (BETA-FIBRIN)

  • 1 April 1987
    • journal article
    • research article
    • Vol. 69  (4) , 1073-1081
Abstract
Release of fibrinopeptide B from fibrinogen by copperhead venom procoagulant enzyme results in a form of fibrin (.beta.-fibrin) with a weaker self-aggregation characteristics than the normal product (.alpha..beta.-fibrin) produced by release of fibrinopeptides A (FPA) and B (FPB) by thrombin. We investigated the ultrastructure of these two types of fibrin as well as that of .beta.-fibrin prepared from fibrinogen Metz (A.alpha.16 Arg .fwdarw. Cys), a homozygous dysfibrinogenemic mutant that does not release FPA. At 14.degree. C and physiologic solvent conditions (0.15 mol/L of NaCl, 0.015 mol/L of Tris buffer pH 7.4), the turbidity (350 nm) of rapidly polymerizing .alpha..beta.-fibrin (thrombin 1 to 2 U/mL) plateaued in < 6 min and formed a "coarse" matrix consisting of anastomosing fiber bundles (mean diameter 92 nm). More slowly polymerizing .alpha..beta.-fibrin (thrombin 0.01 and 0.001 U/mL) surpassed this turbidity after .gtoreq. 60 minutes and concomitantly developed a network of thicker fiber bundles (mean diameters 118 and 186 nm, respectively). Such matrices also contained networks on highly branched, twisting, "fine" fibrils (fiber diameters 7 to 30 nm) that are usually characteristic of matrices formed at high ionic strength and pH. Slowly polymerizing .beta.-fibrin, like slowly polymerizing .alpha..beta.-fibrin, displayed considerable quantities of fine matrix in addition to an underlying thick cable network (mean fiber diameter 135 nm), whereas rapidly polymerizing .beta.-fibrin monomer was comprised almost exclusively of wide, poorly anastomosed, striated cables (mean diameter 212 nm). Metz .beta.-fibrin clots were more fragile than those of normal .beta.-fibrin and were comprised almost entirely of a fine network. Metz fibrin could be induced, however, to form thick fiber bundles (mean diameter 76 nm) in the presence of albumin at a concentration (500 .mu.mol/L) in the physiologic range and resembled a Metz plasma fibrin clot in that regard. The diminished capacity of Metz .beta.-fibrin to form thick fiber bundles may be due to impaired use of occupancy of a polymerization site exposed by FPB release. Our results indicate that twisting fibrils are an inherent structural feature of all forms of assembling fibrin, and suggest that mature .beta.-fibrin or .alpha..beta.-fibrin clots develop from networks of thin fibrils that have the ability to coalesce to form thicker fiber bundles.