STUDIES ON IMMUNE CELLULAR INJURY II. FUNCTIONAL ROLE OF Ctl ESTERASE IN IMMUNE CYTOTOXICITY* BY IRWIN

I t was demonstrated in the preceding paper (1) that incubation of primary isolates of normal human amnion cells with specific rabbit antibody and normal human serum resulted in immune cellular injury as measured by two independent criteria of cytotoxicity. I t was further shown that the factors in normal human serum which were required in addition to specific antibody for production of cytotoxicity were indistinguishable from components of hemolytic complement and calcium and magnesium ions. Thus, no fundamental differences were apparent between requirements for immune injury of human amnion cells (immune cytotoxicity) and immune injury of sheep or human erythrocytes (immune hemolysis) (2, 3). The sequence of action of the components of complement in immune hemolysis was deduced by Pillemer, Seifter, and Ecker (4). In further dissection of this complex system, Mayer, Levine, and their associates showed that early events in immune hemolysis involved reactions between the sensitized erythrocyte and the first and fourth components of complement (C'I and C~4) in the presence of Ca ++ . The resulting complex could then react with the second component of complement (C'2) in the presence of Mg ++, forming a complex which could react with the third component (CI3) in the absence of divalent cations. The latter reaction effected injury of the erythrocyte leading to hemolysis (2). The biochemical as opposed to the descriptive events in immune hemolysis were unknown. A large body of evidence has accumulated from this laboratory and independently from Becker's laboratory that C'I is a proenzyme which may be activated by antigen-antibody reactions (5). The active enzyme is an esterase (C'I esterase) capable of hydrolyzing certain synthetic amino acid esters, such as N-acetyl-L-tyrosine ethyl ester and p-toluenesulfonyl-L-arginine methyl