Evidence that proteases are involved in superoxide production by human polymorphonuclear leukocytes and monocytes.
Evidence that proteases are involved in superoxide production by human polymorphonuclear leukocytes and monocytes.
复制标题
有证据表明蛋白酶参与人类多形核白细胞和单核细胞产生超氧化物。
DOI：
10.1172/jci109662
复制
发表时间：
1980
期刊：
影响因子：
--
通讯作者：
S. Sakamoto
中科院分区：
文献类型：
--
作者：
S. Kitagawa;F. Takaku;S. Sakamoto
用不同的蛋白酶抑制剂和底物探讨了蛋白酶在人多形核白细胞（PMN）和单核细胞产生超氧阴离子（O2-）中的可能作用。丝氨酸蛋白酶的蛋白酶抑制剂和修饰丝氨酸蛋白酶活性位点的合成抑制剂。使用的底物是胰凝乳蛋白酶型以及胰蛋白酶型蛋白酶的合成底物。这些抑制剂和底物均能抑制细胞松弛素E和伴刀豆球蛋白A诱导的人PMN和单核细胞的O2-分泌，但PMN对这些抑制剂和底物的敏感性高于单核细胞。抑制迅速出现，即使当抑制剂被添加在同一时间作为兴奋剂，在“诱导时间的O2-生产”或在最大的O2-生产的时间，而更大的抑制时，观察到的细胞与抑制剂预孵育。这些观察结果表明，酶活性丝氨酸蛋白酶是必不可少的，这些吞噬细胞启动和维持O2-生产的刺激。抑制剂和底物对胰凝乳蛋白酶型蛋白酶的抑制作用大于那些物质对胰蛋白酶型蛋白酶的抑制作用。大分子抑制剂也能抑制O2-的产生。这些结果表明，丝氨酸蛋白酶参与的O2-生产的人PMN和单核细胞类似胰凝乳蛋白酶，而不是胰蛋白酶，并可能位于细胞表面膜。
The possible participation of proteases in superoxide (O2-) production by human polymorphonuclear leukocytes (PMN) and monocytes was explores using various protease inhibitors and substrates. Protease inhibitors of serine proteases and synthetic inhibitors that modify the active site of serine proteases. Substrates used were synthetic substrates of the chymotrypsin type as well as trypsin type of protease. All these inhibitors and substrates inhibited O2- oroduction by human PMN and monocytes induced by cytochalasin E and concanavalin A, though PMN were more sensitive to these inhibitors and substrates than monocytes. Inhibition appeared rapidly even when the inhibitors were added at the same time as the stimulants, during the "induction time of O2-production" or at the time of maximum O2- production, whereas much greater inhibition was observed when the cells were preincubated with the inhibitors. These observations suggest that enzymatically active serine proteases are essential for these phagocytic cells to initiate and maintain the O2- production in response to the stimuli. The inhibitory effect of the inhibitor and substrate for chymotrypsin type protease was greater than that of those substances for trypsin-type protease. Macromolecular inhibitors also inhibited the O2- production. These findings suggest that the serine proteases involved in the O2- production by human PMN and monocytes are similar to chymotrypsin rather than trypsin, and are possibly located at the cell surface membrane.