Abstract
Plasma factor XIIIa (A*2 ) is a regulator in balancing the opposing coagulation and fibrinolytic processes. Its enzymatic activity is to catalyze ε-(γ-glutamyl)lysyl bonds between certain substrate molecules to link them by strong bonds. The primary physiological substrates are crosslinks between the γ and α chains of fibrin that produce γ-γ-dimer and α-polymer, between α2 -plasmin inhibitor (α2 -PI) and α chains of fibrin, and between fibronectin and fibrin. We have characterized a unique factor XIII antibody that is specific for the middle 54-kDa section of A*2 . It does not react with the zymogen (A2 ) or the inactive intermediate (A′2 ), and it does not inhibit the active center, as do most patient antibodies to factor XIII. This antibody inhibits the formation of A*2 -fibrin complexes. Because of this specificity, the antibody was used to study other substrate interactions. It inhibited formation of fibronectin-factor XIIIa complexes, similarly to fibrin, and there was very little crosslinking of fibronectin to a fibrin clot. However, the amount of α2 -PI crosslinked to a fibrin clot was normal. It was concluded that this antibody interferes with exosite binding of fibrin and fibronectin in a similar way, while at least one critical exosite binding domain for α2 -PI is different from those of the other two substrates. Furthermore, with this antibody, it was shown that both α2 -PI-α chain crosslinking and α-polymer formation are necessary to normalize the rate of fibrinolysis.
Key words:
Factor XIIIa - fibrin - fibronectin - α2 -antiplasma - factor XIIIa-substrate complex
