Factors affecting Gamma-Chain Multimer Formation in Cross-Linked Fibrin

Document Type

Article

Publication Date

1-28-1992

Publisher

American Chemical Society

Source Publication

Biochemistry

Source ISSN

0006-2960

Original Item ID

DOI: 10.1021/bi00118a040

Abstract

The major covalently linked multimolecular D fragments found in plasmic digests of factor XHIa cross-linked fibrin formed under physiological pH and ionic strength conditions consist of D dimers, D trimers, and D tetramers. These fragments are linked by {-amino-Υ-glutamyllysine bonds in the carboxy-terminal regions of their Υchains, which had originated in the cross-linked fibrin as Υdimers, Υtrimers, and Υtetramers, respectively. In this study, factors affecting the degree and rate of formation of these three classes of cross-linked Υchains were determined by analyzing the D-fragment content of plasmic digests of cross-linked fibrin that had been sampled after all Υ-chain monomers had been consumed in the cross-linking process. D trimers and D tetramers, expressed as a proportion of the total D-fragment content, both increased at the expense of the D-dimer population as a function of increasing factor XIII concentration, the time of cross-linking, or the CaCl2 concentration. Their levels decreased as the ionic strength was raised by NaCl addition. However, the ionic strength effect could be reversed by concomitantly raising the CaCl2 concentration. Digests of clots prepared from recalcified fresh citrated plasma also contained each type of cross-linked D fragment, and the proportion of D trimers and D tetramers in the digest increased with increasing clot incubation time. These results indicate that Υ-trimer and Υ-tetramer formation is a dynamic physiological process. Such cross-linked trimeric and tetrameric Υ-chain structures may function in vivo to stabilize the fibrin matrix at interfiber contacts and/or at branch points, thereby enhancing mechanical strength, elasticity, and/or clot resistance to fibrinolysis.

Comments

Biochemistry, Vol. 31, No. 3 (January 28, 1992): 936-941. DOI.

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