Thromb Haemostasis
-
Plasma factor XIII (plasma protransglutaminase) circulates as an A2B2 tetramer bound to the gamma' variant chains of fibrinogen "2". During clotting the A subunits of fXIII are cleaved by thrombin to form fXIIIa (transglutaminase) and in the presence of calcium ions, activated A2* subunits dissociate from the B subunits. When purified plasma fXIII or recombinant cellular factor XIII (A2) was incubated with fibrinogen in the presence of calcium ions (> or =50 microM) a non-synerizing gel formed concomitant with formation of gamma dimers, followed by Agamma polymers, and eventually gamma trimers and gamma tetramers. ⋯ The results further indicate that uncleaved fXIII in plasma provides a potent source of readily available crosslinking activity in clotting blood. Fibrinogen 2, whose gamma'chains bind fXIII B subunits, was crosslinked 3.5 times more slowly by fXIII than was fibrinogen 1 (lacking gamma' chains), suggesting that complex formation between fibrinogen 2 and plasma fXIII plays a significant role in down-regulating potential plasma fXIII-mediated crosslinking activity. Since fibrin is a considerably better substrate for fXIII than is fibrinogen, the rate at which crosslinking takes place in a fibrinogen-containing plasma environment is much lower than it would be if fibrin were present.