Inhibition of human natural cytotoxicity by macromolecular antiproteases.
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 apha 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.
D000818:Animals; D002417:Cattle; D002918:Chymotrypsin / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D046911:Macromolecular Substances; D011480:Protease Inhibitors / Q000276:immunology*; D012710:Serum Albumin, Bovine; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
D046911:Macromolecular Substances; D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; D012710:Serum Albumin, Bovine; D002918:Chymotrypsin