Evidence that α2-Antiplasmin Becomes Covalently Ligated to Plasma Fibrinogen in the Circulation: a New Role for Plasma Factor XIII in Fibrinolysis Regulation

Authors

Michael W. Mosesson, Blood Center of WisconsinFollow
Kevin R. Siebenlist, Marquette UniversityFollow
Irene Hernandez, Blood Research InstituteFollow
K. N. Lee, University of Oklahoma Health Sciences Center
V. J. Christiansen, University of Oklahoma Health Sciences Center
P. A. McKee, University of Oklahoma Health Sciences Center

Document Type

Article

Publication Date

9-2008

Publisher

Wiley

Source Publication

Journal of Thrombosis and Haemostasis

Source ISSN

1538-7933

Original Item ID

DOI: 10.1111/j.1538-7836.2008.03056.x

Abstract

Background:

Plasma alpha₂-antiplasmin (α₂AP) is a rapid and effective inhibitor of the fibrinolytic enzyme plasmin. Congenital α₂AP 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), α₂AP 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 α₂AP 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 α₂AP into fibrinogen in the circulation.

Results and Conclusions:

We now provide evidence that FXIII incorporates I¹²⁵-labelled α₂AP into the Aα-chain sites on fibrinogen or fibrin. We also measured the content of α₂AP 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 α₂AP 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.

Comments

Accepted version. Journal of Thrombosis and Haemostasis (JTH), Vol. 6, No. 9 (September 2008): 1565-1570. DOI. © 2008 Wiley. Used with permission.

Recommended Citation

Mosesson, Michael W.; Siebenlist, Kevin R.; Hernandez, Irene; Lee, K. N.; Christiansen, V. J.; and McKee, P. A., "Evidence that α2-Antiplasmin Becomes Covalently Ligated to Plasma Fibrinogen in the Circulation: a New Role for Plasma Factor XIII in Fibrinolysis Regulation" (2008). Biomedical Sciences Faculty Research and Publications. 217.
https://epublications.marquette.edu/biomedsci_fac/217