Abstract Human natural cell-mediated cytotoxicity is inhibited by macromolecular protease inhibitors. Human plasma alpha  1 antiproteases are more effective than the plant antiproteases lima bean trypsin inhibitor and soybean trypsin inhibitor for reduction of cytotoxicity to the "slow" targets T24 human bladder carcinoma and NKI-1 melanoma. This inhibition of natural cytotoxicity is more readily demonstrable in serum-free medium containing crystalline bovine serum albumin than in medium containing fetal calf serum. Although electrophoretically homogeneous plasma alpha  1 antitrypsin inhibits natural cytotoxicity, partially purified alpha  1 antitrypsin preparations that contain several alpha  1 proteins are more inhibitory at equivalent trypsin inhibitory capacities. Partially purified alpha  1 antichymotrypsin with no antitrypsin activity is an extremely potent inhibitor. Thus, it seems likely that several of the plasma antiproteases, including alpha  1 antitrypsin and alpha  1 antichymotrypsin, are capable of influencing natural cytotoxicity. These data indicate that serine-dependent proteases hae a critical role in triggering and/or effecting cell-mediated cytolysis. Furthermore, since alpha  1 antichymotrypsin and alpha  1 antitrypsin are acute phase proteins, the increase in plasma concentration or turnover rates of the proteins could influence natural killer cell activity in vivo.

Hudig, D., Haverty, T., Fulcher, C., Redelman, D., & Mendelsohn, J. (1981). Inhibition of human natural cytotoxicity by macromolecular antiproteases. The Journal of Immunology, 126(4), 1569–1574.