Human Factor XIII from Plasma and Platelets

Abstract

The subunit structures of Factor XIII from plasma and platelets have been examined by sedimentation equilibrium in the ultracentrifuge. Plasma Factor XIII has a molecular weight of 320,000 ± 20,000 in dilute salt solution at neutral pH. The two different types of subunits of the plasma factor, the a and b chains, have molecular weights of about 75,000 and 88,000, respectively. Platelet Factor XIII has a molecular weight of 146,000 ± 10,000, whereas its single type of subunit, the a chain, has a molecular weight of about 75,000. The a chains of the platelet and plasma factors are identical not only in molecular weight but also on gel electrophoresis in three different systems and in amino acid composition. The a chain of platelet Factor XIII combines with the b chain of plasma factor to give a protein which is electrophoretically indistinguishable from native plasma Factor XIII. In addition, the amino acid composition of the plasma factor is essentially identical with twice the average amino acid composition of the a and b chains. These analyses indicate that the subunit structure of plasma factor is a2b2 and that of the platelet factor is a2. The subunits of each factor are combined in the native molecules solely by noncovalent bonds. Thrombin, trypsin, reptilase, papain, and an enzyme contaminating some ancrod preparations activate plasma Factor XIII. In each case, except possibly with papain, Factor XIII activation coincides with a decrease in molecular weight of 4,000 of the a chain. High concentrations of thrombin only slightly inactivate Factor XIII after prolonged incubation, whereas trypsin not only activates but extensively inactivates plasma Factor XIII. Activation of Factor XIII is not autocatalyt c. Neither release of the fibrinopeptides nor gelation is required for activated plasma Factor XIII to cross-link fibrinogen. The γ chains of fibrin are cross-linked by activated plasma Factor XIII more rapidly than the α chains, but the rates of cross-linking of the α (A) and γ chains of fibrinogen are about the same. In addition, the pattern of cross-linking of fibrinogen or fibrin by guinea pig liver transglutaminase is different from that catalyzed by activated Factor XIII. The lysis time of fibrin clots with cross-linked α and γ chains was considerably greater than that of fibrin clots containing cross-linked γ chains but little or no cross-linked α chains.