The role of γA/γ' fibrinogen in plasma factor XIII activation

Maia Moaddel, Lisa A. Falls, David Farrell

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Factor XIII zymogen activation is a complex series of events that involve fibrinogen acting in several different roles. This report focuses on the role of fibrinogen as a cofactor in factor XIII activation by thrombin. We demonstrate that fibrinogen has two distinct activities that lead to an increased rate of factor XIII activation. First, the thrombin proteolytic activity is increased by fibrin. The cleavage rates of both a small chromogenic substrate and the factor XIII activation peptide are increased in the presence of either the major fibrin isoform, γA/γA fibrin, or a minor variant form, γA/γ' fibrin. This enhancement of thrombin activity by fibrin is independent of fibrin polymerization and requires only cleavage of the fibrinopeptides. Subsequently, γA/γ' fibrinogen accelerates plasma factor XIII activation by a non-proteolytic mechanism. This increased rate of activation results in a slightly more rapid cross-linking of fibrin γA and γ' chains and a significantly more rapid cross-linking of fibrin α chain multimers. Together, these results show that although both forms of fibrin increase the rate of activation peptide cleavage by thrombin, γA/γ' fibrinogen also increases the rate of factor XIII activation in a non-proteolytic manner. A revised model of factor XIII activation is presented below.

Original languageEnglish (US)
Pages (from-to)32135-32140
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number41
StatePublished - Oct 13 2000

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Factor XIII
Fibrin
Fibrinogen
Chemical activation
Plasmas
Thrombin
Chromogenic Compounds
Enzyme Precursors
Polymerization
Protein Isoforms
Peptides

ASJC Scopus subject areas

  • Biochemistry

Cite this

The role of γA/γ' fibrinogen in plasma factor XIII activation. / Moaddel, Maia; Falls, Lisa A.; Farrell, David.

In: Journal of Biological Chemistry, Vol. 275, No. 41, 13.10.2000, p. 32135-32140.

Research output: Contribution to journalArticle

Moaddel, Maia ; Falls, Lisa A. ; Farrell, David. / The role of γA/γ' fibrinogen in plasma factor XIII activation. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 41. pp. 32135-32140.
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