Release of alpha 2-plasmin inhibitor from plasma fibrin clots by activated coagulation factor XIII. Its effect on fibrinolysis.
When blood coagulation takes place in the presence of calcium ions, alpha 2-plasmin inhibitor (alpha 2PI) is cross-linked to fibrin by activated coagulation Factor XIII (XIIIa) and thereby contributes to the resistance of fibrin to fibrinolysis. It was previously shown that the cross-linking reaction is a reversible one, since the alpha 2PI-fibrinogen cross-linked complex could be dissociated. In the present study we have shown that the alpha 2PI-fibrin cross-linking reaction is also a reversible reaction and alpha 2PI which had been cross-linked to fibrin can be released from fibrin by disrupting the equilibrium, resulting in a decrease of its resistance to fibrinolysis. When the fibrin clot formed from normal plasma in the presence of calcium ions was suspended in alpha 2PI-deficient plasma of buffered saline, alpha 2PI was gradually released from fibrin on incubation. When alpha 2PI was present in the suspending milieu, the release was decreased inversely to the concentrations of alpha 2PI in the suspending milieu. The release was accelerated by supplementing XIIIa or the presence of a high concentration of the NH2-terminal 12-residue peptide of alpha 2PI (N-peptide) which is cross-linked to fibrin in exchange for the release of alpha 2PI. When the release of alpha 2PI from fibrin was accelerated by XIIIa or N-peptide, the fibrin became less resistant to the fibrinolytic process, resulting in an acceleration of fibrinolysis which was proportional to the degree of the release of alpha 2PI. These results suggest the possibility that alpha 2PI could be released from fibrin in vivo by disrupting the equilibrium of the alpha 2PI-fibrin cross-linking reaction, and that the release would result in accelerated thrombolysis.
J
J
Mimuro
S
S
Kimura
N
N
Aoki
D004591:Electrophoresis, Polyacrylamide Gel; D005176:Factor XIII / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis; D006801:Humans; D007700:Kinetics; D010446:Peptide Fragments / Q000494:pharmacology; D000979:alpha-2-Antiplasmin / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000378:metabolism*
D010446:Peptide Fragments; D000979:alpha-2-Antiplasmin; D000511:alpha-Macroglobulins; D005337:Fibrin; D005176:Factor XIII