Warheit D B, Carakostas M C, Bamberger J R, Hartsky M A
Central Research and Development, Haskell Laboratory for Toxicology and Industrial Medicine, E.I. du Pont de Nemours and Company, Newark, Delaware 19714.
Environ Res. 1991 Dec;56(2):186-203. doi: 10.1016/s0013-9351(05)80008-8.
Complement-mediated mechanisms are known to play a role in pulmonary inflammation and clearance responses to some types of inhaled particles. The present studies were undertaken to investigate the role of complement in mediating pulmonary inflammation and/or phagocytosis as a function of particle clearance in rats exposed to silica or carbonyl iron (CI) particles. Both particle types were shown to be weak activators of serum complement in vitro. In these studies, normal and complement-depressed (CVF-treated) rats were exposed to aerosols of CI or silica particles for 6 hr at 100 mg/m3. Following exposure, alveolar fluids and cells from sham and dust-exposed animals were recovered by bronchoalveolar lavage (BAL) at several time periods postexposure and measured for a variety of biochemical and cellular indices. In addition, pulmonary macrophages were cultured and studied for morphology and phagocytosis. Our results showed that CI exposure did not produce cellular or biochemical indices of pulmonary inflammation, either in normal or complement-depleted rats. However, fewer phagocytic macrophages were recovered from the lungs of CVF-treated, CI-exposed rats than from normal exposed animals. In contrast, silica inhalation produced a sustained PMN inflammatory response in the lungs of exposed rats, measured up through 1 month postexposure, along with significant increases in BAL fluid levels of LDH, protein, and alkaline phosphatase (P less than 0.05) and deficits in pulmonary macrophage phagocytic functions. Cobra venom factor (CVF) treatment prior to exposure in rats had no significant effect upon the silica-induced parameters, suggesting that complement may not play an important role in the acute pulmonary response to silica. The results indicate that complement may play a role in mediating CI-related macrophage clearance responses but has little effect upon sustained silica-induced pulmonary inflammatory parameters.
已知补体介导的机制在肺部炎症以及对某些类型吸入颗粒的清除反应中发挥作用。本研究旨在探讨补体在介导肺部炎症和/或吞噬作用中所起的作用，这是暴露于二氧化硅或羰基铁（CI）颗粒的大鼠颗粒清除功能的一个方面。两种颗粒类型在体外均显示为血清补体的弱激活剂。在这些研究中，正常大鼠和补体缺乏（经眼镜蛇毒因子处理）的大鼠在100 mg/m³的浓度下暴露于CI或二氧化硅颗粒气溶胶6小时。暴露后，在暴露后的几个时间段通过支气管肺泡灌洗（BAL）回收假手术组和粉尘暴露动物的肺泡液和细胞，并测量各种生化和细胞指标。此外，对肺巨噬细胞进行培养并研究其形态和吞噬作用。我们的结果表明，无论是正常大鼠还是补体缺乏的大鼠，暴露于CI均未产生肺部炎症的细胞或生化指标。然而，与正常暴露动物相比，经眼镜蛇毒因子处理且暴露于CI的大鼠肺中回收的吞噬性巨噬细胞较少。相反，吸入二氧化硅在暴露大鼠的肺中产生了持续的中性粒细胞炎症反应，在暴露后长达1个月的时间内均可检测到，同时BAL液中乳酸脱氢酶、蛋白质和碱性磷酸酶水平显著升高（P<0.05），并且肺巨噬细胞吞噬功能出现缺陷。在大鼠暴露前用眼镜蛇毒因子（CVF）处理对二氧化硅诱导的参数没有显著影响，这表明补体可能在对二氧化硅的急性肺部反应中不起重要作用。结果表明，补体可能在介导与CI相关的巨噬细胞清除反应中发挥作用，但对二氧化硅诱导的持续肺部炎症参数影响很小。
