Acceleration of fibrinolysis by the N-terminal peptide of alpha 2-plasmin inhibitor.
When blood plasma containing the NH2-terminal 12-residue peptide (N-peptide) of alpha 2-plasmin inhibitor (alpha 2PI; alpha 2-antiplasmin) was clotted in the presence of calcium ions, the N-peptide and alpha 2PI were cross-linked to fibrin by activated coagulation factor XIII. The amount of N-peptide cross-linked to fibrin was proportional to the concentration of N-peptide present in plasma. On the other hand, the amount of alpha 2PI cross-linked to fibrin was decreased by the presence of N-peptide, and the decrease was in reverse relationship to the increase of cross-linking of N-peptide. Spontaneous fibrinolysis or fibrinolysis induced by tissue plasminogen activator was accelerated by the presence of N-peptide, and the acceleration was dependent on the concentrations of N-peptide and directly proportional to inhibition of alpha 2PI cross-linking exerted by N-peptide. The acceleration was more pronounced when the clot was compacted by platelet-mediated clot retraction or by a squeeze. Fibrinolysis of an alpha 2PI-deficient or a factor XIII-deficient plasma clot was not accelerated by N-peptide. These findings were substantiated in a purified system and support the previous proposal that alpha 2PI is cross-linked to fibrin at the glutamine residue that is next to the NH2-terminus of alpha 2PI, and this factor XIII-mediated cross-linking of alpha 2PI is significant in inhibition of physiologically occurring endogenous fibrinolysis.
Kimura
S
S
Tamaki
T
T
Aoki
N
N
D005337:Fibrin / Q000378:metabolism; D005341:Fibrinolysin / Q000037:antagonists & inhibitors*; D005342:Fibrinolysis; D006801:Humans; D066298:In Vitro Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000097:blood* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D013329:Structure-Activity Relationship; D000979:alpha-2-Antiplasmin / Q000494:pharmacology*
D010446:Peptide Fragments; D011480:Protease Inhibitors; D000979:alpha-2-Antiplasmin; D005337:Fibrin; D005341:Fibrinolysin