TY - JOUR
T1 - The role of γA/γ' fibrinogen in plasma factor XIII activation
AU - Moaddel, Maia
AU - Falls, Lisa A.
AU - Farrell, David H.
PY - 2000/10/13
Y1 - 2000/10/13
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M000496200
DO - 10.1074/jbc.M000496200
M3 - Article
C2 - 10913112
AN - SCOPUS:0034644660
SN - 0021-9258
VL - 275
SP - 32135
EP - 32140
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 41
ER -