Hudig D, Haverty T, Fulcher C, Redelman D, Mendelsohn J
J Immunol. 1981 Apr;126(4):1569-74.
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.
大分子蛋白酶抑制剂可抑制人类自然细胞介导的细胞毒性。人血浆α1抗蛋白酶在降低对“慢速”靶标T24人膀胱癌和NKI - 1黑色素瘤的细胞毒性方面比植物抗蛋白酶利马豆胰蛋白酶抑制剂和大豆胰蛋白酶抑制剂更有效。在含有结晶牛血清白蛋白的无血清培养基中比在含有胎牛血清的培养基中，这种对自然细胞毒性的抑制作用更容易得到证实。虽然电泳纯的血浆α1抗胰蛋白酶可抑制自然细胞毒性，但含有几种α1蛋白的部分纯化的α1抗胰蛋白酶制剂在同等胰蛋白酶抑制能力下具有更强的抑制作用。没有抗胰蛋白酶活性的部分纯化的α1抗糜蛋白酶是一种极其有效的抑制剂。因此，似乎包括α1抗胰蛋白酶和α1抗糜蛋白酶在内的几种血浆抗蛋白酶都能够影响自然细胞毒性。这些数据表明，丝氨酸依赖性蛋白酶在触发和/或实现细胞介导的细胞溶解中起关键作用。此外，由于α1抗糜蛋白酶和α1抗胰蛋白酶是急性期蛋白，这些蛋白血浆浓度或周转率的增加可能会影响体内自然杀伤细胞的活性。
