Sibille Y, Merrill W W, Cooper J A, Polomski L, Gee J B
Am Rev Respir Dis. 1984 Jul;130(1):110-4. doi: 10.1164/arrd.1984.130.1.110.
Certain chloromethyl ketone (CH2Cl) protease inhibitors diminish PMA-stimulated (phorbol myristate acetate) superoxide (O-2) release by both human alveolar macrophages (HAM) and polymorphonuclear leukocytes (PMN). Additionally, these compounds diminish glutathione reductase activity (GSSR) and intracellular levels of reduced glutathione (GSH). Inhibitory profiles of these molecules were similar for each of the measured cell products, i.e., TPCK = Z Gly-Leu-Phe-CH2Cl greater than TLCK greater than Meo Succ-(Ala)2-Pro-Val-CH2Cl. Because Meo Succ-(Ala)2-Pro-Val inhibited GSSR in cell sonicates but not in intact cells, it appears that all these effects are closely related to the cell penetration by these CH2Cl compounds. We conclude that (1) inhibition of O-2 release in PMN and HAM by CH2Cl does not necessarily implicate a surface protease in O-2 production, (2) some of these compounds certainly impair the intracellular glutathione redox system necessary for the respiratory burst, and (3) only the nonpenetrating inhibitor Meo Succ-(Ala)2-Pro-Val-CH2Cl can be used to distinguish injury caused by extracellular protease (elastase) from that caused by superoxide anion.
某些氯甲基酮（CH2Cl）蛋白酶抑制剂可减少佛波酯（PMA，十四酰佛波醇乙酯）刺激的人肺泡巨噬细胞（HAM）和多形核白细胞（PMN）的超氧化物（O-2）释放。此外，这些化合物还会降低谷胱甘肽还原酶活性（GSSR）和细胞内还原型谷胱甘肽（GSH）的水平。对于每种被测细胞产物，这些分子的抑制谱相似，即TPCK = Z甘氨酰-亮氨酰-苯丙氨酸-CH2Cl＞TLCK＞甲氧基琥珀酰-（丙氨酸）2-脯氨酰-缬氨酸-CH2Cl。由于甲氧基琥珀酰-（丙氨酸）2-脯氨酰-缬氨酸在细胞超声裂解物中可抑制GSSR，但在完整细胞中则不能，因此似乎所有这些效应都与这些CH2Cl化合物的细胞穿透密切相关。我们得出以下结论：（1）CH2Cl对PMN和HAM中O-2释放的抑制不一定意味着O-2产生过程中有表面蛋白酶参与；（2）这些化合物中的一些肯定会损害呼吸爆发所需的细胞内谷胱甘肽氧化还原系统；（3）只有非穿透性抑制剂甲氧基琥珀酰-（丙氨酸）2-脯氨酰-缬氨酸-CH2Cl可用于区分细胞外蛋白酶（弹性蛋白酶）和超氧阴离子所造成的损伤。
