ANNEXIN-II TETRAMER INHIBITS PLASMIN-DEPENDENT FIBRINOLYSIS

In this paper, we have characterized the regulation of plasmin activit y by annexin II tetramer (AIIt). Plasmin activity was measured by a fi brin lysis assay in which a fibrin polymer was produced from purified components and the extent of polymer lysis was determined by following changes in turbidity. Extrinsic lysis of the fibrin polymer, initiate d by addition of tissue plasminogen activator (t-FA), was totally blac ked if AIIt was present during fibrin polymer formation. Furthermore, fibrin polymer formed in the presence of AIIt was resistant to extrins ic lysis initiated by addition of plasmin. AIIt bound to fibrin polyme r under conditions in which polymer lysis was inhibited. Plasmin-depen dent extrinsic lysis of the fibrin polymer was also blocked if AIIt wa s present in the incubation medium, and under these conditions the ami dolytic activity of plasmin, measured with an artificial substrate, wa s inhibited about 5-fold. In contrast, in the absence of fibrin, and a t an AIIt/plasmin molar ratio of 526, the amidolytic activity of plasm in was inhibited by only 22.3% +/- 7.4% (mean +/- SD, n = 5) by AIIt. Plasmin-dependent fibrinolysis was only slightly inhibited if fibrin p olymer was formed in the presence of annexins I, II, V, or VI. These r esults identify AIIt as an in vitro regulator of plasmin activity.