Evidence that alpha2-antiplasmin becomes covalently ligated to plasma fibrinogen in the circulation: a new role for plasma factor XIII in fibrinolysis regulation.
BACKGROUND
Plasma alpha2-antiplasmin (alpha2AP) is a rapid and effective inhibitor of the fibrinolytic enzyme plasmin. Congenital alpha2AP 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), alpha2AP becomes covalently ligated to the distal alpha chains of fibrin or fibrinogen at lysine 303 (two potential sites per molecule). Some time ago we showed that alpha2AP 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 alpha2AP into fibrinogen in the circulation.


CONCLUSIONS
We now provide evidence that FXIII incorporates I 125-labelled alpha2AP into the Aalpha-chain sites on fibrinogen or fibrin. We also measured the content of alpha2AP 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 alpha2AP 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.
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA. michael.mosesson@bcw.edu
M W
MW
Mosesson
K R
KR
Siebenlist
I
I
Hernandez
K N
KN
Lee
V J
VJ
Christiansen
P A
PA
McKee
D004797:Enzyme-Linked Immunosorbent Assay; D005176:Factor XIII / Q000502:physiology*; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D007118:Immunoassay; D000979:alpha-2-Antiplasmin / Q000378:metabolism*
D000979:alpha-2-Antiplasmin; D005337:Fibrin; D005340:Fibrinogen; D005176:Factor XIII