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Evidence that α2‐antiplasmin becomes covalently ligated to plasma fibrinogen in the circulation: a new role for plasma factor XIII in fibrinolysis regulation
Author(s) -
MOSESSON M. W.,
SIEBENLIST K. R.,
HERNANDEZ I.,
LEE K. N.,
CHRISTIANSEN V. J.,
MCKEE P. A.
Publication year - 2008
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2008.03056.x
Subject(s) - fibrinogen , fibrin , fibrinolysis , plasmin , chemistry , factor xiii , covalent bond , biochemistry , thrombin , medicine , platelet , immunology , enzyme , biology , organic chemistry
Summary. Background : Plasma alpha 2 ‐antiplasmin (α 2 AP) is a rapid and effective inhibitor of the fibrinolytic enzyme plasmin. Congenital α 2 AP deficiency results in a severe hemorrhagic disorder due to accelerated fibrinolysis. It is well established that in the presence of thrombin‐activated factor XIII (FXIIIa), α 2 AP becomes covalently ligated to the distal α chains of fibrin or fibrinogen at lysine 303 (two potential sites per molecule). Some time ago we showed that α 2 AP is covalently linked to plasma fibrinogen . That singular observation led to our hypothesis that native plasma factor XIII (FXIII), which is known to catalyze covalent cross‐linking of fibrinogen in the presence of calcium ions, can also incorporate α 2 AP into fibrinogen in the circulation. Results and Conclusions : We now provide evidence that FXIII incorporates I 125 ‐labelled α 2 AP into the Aα‐chain sites on fibrinogen or fibrin. We also measured the content of α 2 AP in isolated plasma fibrinogen fractions by ELISA and found that substantial amounts were present (1.2–1.8 moles per mole fibrinogen). We propose that α 2 AP becomes ligated to fibrinogen while in the circulation through the action of FXIII, and that its immediate presence in plasma fibrinogen contributes to regulation of in vivo fibrinolysis.