Drumm K, Buhl R, Kienast K
Department of Physiology, University of Würzburg, Röntgenring 9, D-97070 Würzburg, Germany.
Eur J Med Res. 1999 Feb 25;4(2):59-66.
Soot particles, asbestos fibres and irritant gas are common air pollutants which are able to induce lung and airway pulmonary injury. The aim of this study was to investigate the effect of a simultaneous NO2 and particle or fibre exposure on the proinflammatory specific mRNA expression and protein secretion of human alveolar macrophages (AM) in comparison to only particle or fibre exposed AM. AM were simultaneously exposed to FR 101, P 90, TiO2 or Chrysotile B at a concentration of 100 microg/10(6) cells and to NO2 at a concentration of 1.0 ppm for 30 min. Particle or fibre exposure of the AM was continued in humidified air at 5% CO2 and 37 degrees C for an additional hour (harvesting of total RNA) or additional 7 hrs (harvesting of culture supernatant). The mRNA expression of the proinflammatory cytokines IL-1beta, IL-6, IL-8 and TNF-alpha of NO2-particle/fibre co-exposed AM and only particle or fibre exposed AM was detected using specific RT-PCR. IL-1beta-, IL-6-, IL-8- and TNF-alpha-specific protein secretion was measured by ELISA. Cytotoxicity was detected by lactatedehydrogenase quantification in the culture supernatant. We observed an increased IL-1beta-, IL-6-, IL-8- and TNF-alpha-specific mRNA expression of particle or fibre exposed AM, which was decreased after an additional NO2 exposure. Also the particle or fibre exposure induced significant increase in IL-1beta-, IL-6-, IL-8 and TNF-alpha-release of AM which was decreased after an additional NO2 exposure (p <0.031). The relative cytotoxicity of the NO2-particle/fibre co-exposure was higher than the particle or fibre induced cytotoxicity, but mostly <10%. Therefore it is concluded that particle or fibre exposure may result in an increase in proinflammatory cytokine release by AM, which may be decreased by toxic NO2 due to the oxidative potential (e.g. lipidperoxydation) of this irritant gas. Particle, asbestos fibre and irritant gas exposure may induce airway and pulmonary injury by the activation of AM and consecutive proinflammatory cytokine release.
煤烟颗粒、石棉纤维和刺激性气体是常见的空气污染物，它们能够诱发肺部和气道的肺损伤。本研究的目的是调查与仅暴露于颗粒或纤维的肺泡巨噬细胞（AM）相比，同时暴露于二氧化氮和颗粒或纤维对人肺泡巨噬细胞促炎特异性mRNA表达和蛋白质分泌的影响。将AM同时暴露于浓度为100微克/10⁶个细胞的FR 101、P 90、二氧化钛或温石棉B以及浓度为1.0 ppm的二氧化氮中30分钟。然后将AM在含5%二氧化碳、37℃的潮湿空气中继续暴露于颗粒或纤维中1小时（用于收获总RNA）或额外暴露7小时（用于收获培养上清液）。使用特异性逆转录聚合酶链反应（RT-PCR）检测同时暴露于二氧化氮-颗粒/纤维的AM以及仅暴露于颗粒或纤维的AM中促炎细胞因子白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和肿瘤坏死因子-α（TNF-α）的mRNA表达。通过酶联免疫吸附测定（ELISA）测量IL-1β、IL-6、IL-8和TNF-α特异性蛋白质分泌。通过测定培养上清液中的乳酸脱氢酶来检测细胞毒性。我们观察到暴露于颗粒或纤维的AM中IL-1β、IL-6、IL-8和TNF-α特异性mRNA表达增加，在额外暴露于二氧化氮后这种表达降低。颗粒或纤维暴露还诱导AM中IL-1β、IL-6、IL-8和TNF-α释放显著增加，在额外暴露于二氧化氮后这种释放降低（p<0.031）。二氧化氮-颗粒/纤维共同暴露的相对细胞毒性高于颗粒或纤维诱导的细胞毒性，但大多<10%。因此得出结论，颗粒或纤维暴露可能导致AM促炎细胞因子释放增加，而由于这种刺激性气体的氧化潜能（如脂质过氧化），有毒的二氧化氮可能会使其降低。颗粒、石棉纤维和刺激性气体暴露可能通过激活AM和随后促炎细胞因子的释放而诱发气道和肺损伤。
