STUDIES OF THE PLASMIN SYSTEM II. INHIBITION OF PLASMIN BY SERIrM OR PLASMA* BY PHILIP S. NORMAN,~ M.D

A rather slow, temperature-dependent inhibition was described by Guest, Daly, Ware, and Seegers (1), as well as by Ungar and Damgaard (2). On the other hand, Shulman (3), Jacobsson (4), and Thomas and Dingle (5) have reported rapid and apparently stoichiometric reactions that did not particularly depend on temperature. Grob (6) found a rapid but reversible inhibition of plasmin by serum and, more recently, Shulman (7) isolated a low molecular weight inhibitor from plasma and urine which also reacted rapidly and reversibly, but which accounted for only a small portion of inhibitor activity of whole plasma. Meyers and Burdon found that the variations in proteolytic activity of dilutions of whole serum activated by streptokinase suggested a dissociable inhibitor (8). These apparently conflicting observations may be reconciled by the suggestion of Ratnoff that there are several plasmin inhibitors in blood with differing actions (9). Subsequently, Ratnoff, Lepow, and Pillemer have given evidence for at least three inhibitors in plasma. In their experiments, one plasma component was destroyed by heating at 56 ° for 30 minutes. The remaining heatstable inhibitor they further subdivided on the basis that part of the inhibitory power was inactivated by ammonia and primary amines, leaving a component stable to both heat and these chemicals (10).