Zay K, Devine D, Churg A
Department of Pathology, University of British Columbia, Vancouver, Canada.
J Appl Physiol (1985). 1995 Jan;78(1):53-8. doi: 10.1152/jappl.1995.78.1.53.
Occupational exposure to some types of mineral particles has been shown to be associated with the development of emphysema, but the mechanism of this process is unknown. Because many mineral particles are known to catalyze the formation of active oxygen species in aqueous solution, we hypothesized that mineral particles could oxidatively inactive antiproteinases, leading to an imbalance between protease and antiprotease activities, events similar to those believed to occur with cigarette smoke. To test this hypothesis, human alpha 1-antiproteinase (alpha 1-AP) was incubated with suspensions of freshly ground or aged quartz, and antiproteolytic activity was determined by using porcine pancreatic elastase. Increasing concentrations of quartz were associated with increasing losses of antiproteolytic activity; this effect could be prevented by catalase. Freshly ground quartz was more active than aged quartz. Western blot analysis for alpha 1-AP showed abnormal banding, suggesting that porcine pancreatic elastase-alpha 1-AP complex formation was impaired by silica exposure. Chemical assay of aqueous quartz suspensions demonstrated production of hydrogen peroxide; incubation of alpha 1-AP with hydrogen peroxide caused a dose-dependent loss of antiproteolytic activity, and this also could be prevented by catalase. We conclude that, at least in vitro, quartz can inactivate alpha 1-AP through a hydrogen peroxide-mediated mechanism and that oxidative loss of antiproteinase activity could play a role in mineral dust-induced emphysema.
职业接触某些类型的矿物颗粒已被证明与肺气肿的发生有关，但这一过程的机制尚不清楚。由于已知许多矿物颗粒能催化水溶液中活性氧的形成，我们推测矿物颗粒可能使抗蛋白酶氧化失活，导致蛋白酶和抗蛋白酶活性失衡，这一情况类似于人们认为与香烟烟雾有关的情况。为了验证这一假设，将人α1-抗蛋白酶（α1-AP）与新鲜研磨或老化的石英悬浮液孵育，并用猪胰弹性蛋白酶测定抗蛋白水解活性。石英浓度增加与抗蛋白水解活性损失增加相关；过氧化氢酶可防止这种效应。新鲜研磨的石英比老化的石英更具活性。对α1-AP的蛋白质印迹分析显示条带异常，表明二氧化硅暴露会损害猪胰弹性蛋白酶-α1-AP复合物的形成。对石英水悬浮液的化学分析表明产生了过氧化氢；将α1-AP与过氧化氢孵育会导致抗蛋白水解活性呈剂量依赖性丧失，这也可被过氧化氢酶阻止。我们得出结论，至少在体外，石英可通过过氧化氢介导的机制使α1-AP失活，抗蛋白酶活性的氧化损失可能在矿物粉尘诱导的肺气肿中起作用。
