Bachoual Rafik, Boczkowski Jorge, Goven Delphine, Amara Nadia, Tabet Lyes, On Dinhill, Leçon-Malas Véronique, Aubier Michel, Lanone Sophie
Inserm, U700 Université Paris 7 Denis Diderot, site Bichat, and Biochimie B, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France.
Chem Res Toxicol. 2007 Oct;20(10):1426-33. doi: 10.1021/tx700093j. Epub 2007 Sep 21.
Particulate matter (PM) from atmospheric pollution can easily deposit in the lungs and induce recruitment of inflammatory cells, a source of inflammatory cytokines, oxidants, and matrix metalloproteases (MMPs), which are important players in lung structural homeostasis. In many large cities, the subway system is a potent source of PM emission, but little is known about the biological effects of PM from this source. We performed a comprehensive study to evaluate the biological effects of PM sampled at two sites (RER and Metro) in the Paris subway system. Murine macrophages (RAW 264.7) and C57Bl/6 mice, respectively, were exposed to 0.01-10 microg/cm2 and 5-100 microg/mouse subway PM or reference materials [carbon black (CB), titanium dioxide (TiO2), or diesel exhaust particles (DEPs)]. We analyzed cell viability, production of cellular and lung proinflammatory cytokines [tumor necrosis factor alpha (TNFalpha), macrophage inflammatory protein (MIP-2), KC (the murin analog of interleukin-8), and granulocyte macrophage-colony stimulating factor (GM-CSF)], and mRNA or protein expression of MMP-2, -9, and -12 and heme oxygenase-1 (HO-1). Deferoxamine and polymixin B were used to evaluate the roles of iron and endotoxin, respectively. Noncytotoxic concentrations of subway PM (but not CB, TiO2, or DEPs) induced a time- and dose-dependent increase in TNFalpha and MIP-2 production by RAW 264.7 cells, in a manner involving, at least in part, PM iron content (34% inhibition of TNF production 8 h after stimulation of RAW 264.7 cells with 10 microg/cm2 RER particles pretreated with deferoxamine). Similar increased cytokine production was transiently observed in vivo in mice and was accompanied by an increased neutrophil cellularity of bronchoalveolar lavage (84.83+/-0.98% of polymorphonuclear neutrophils for RER-treated mice after 24 h vs 7.33+/-0.99% for vehicle-treated animals). Subway PM induced an increased expression of MMP-12 and HO-1 both in vitro and in vivo. PM from the Paris subway system has transient biological effects. Further studies are needed to better understand the pathophysiological implications of these findings.
大气污染中的颗粒物（PM）可轻易沉积在肺部，引发炎症细胞的募集，这些炎症细胞是炎症细胞因子、氧化剂和基质金属蛋白酶（MMPs）的来源，而它们在肺结构稳态中起着重要作用。在许多大城市，地铁系统是PM排放的一个重要来源，但人们对该来源的PM的生物学效应知之甚少。我们进行了一项全面研究，以评估在巴黎地铁系统两个站点（区域快铁和地铁）采集的PM的生物学效应。分别将小鼠巨噬细胞（RAW 264.7）和C57Bl/6小鼠暴露于0.01 - 10微克/平方厘米和5 - 100微克/只的地铁PM或参考物质[炭黑（CB）、二氧化钛（TiO2）或柴油机尾气颗粒（DEPs）]。我们分析了细胞活力、细胞和肺促炎细胞因子[肿瘤坏死因子α（TNFα）、巨噬细胞炎性蛋白（MIP - 2）、KC（白细胞介素 - 8的小鼠类似物）和粒细胞巨噬细胞集落刺激因子（GM - CSF）]的产生，以及MMP - 2、 - 9和 - 12和血红素加氧酶 - 1（HO - 1）的mRNA或蛋白表达。分别使用去铁胺和多粘菌素B评估铁和内毒素的作用。地铁PM的非细胞毒性浓度（但不是CB、TiO2或DEPs）可诱导RAW 264.7细胞中TNFα和MIP - 2的产生呈时间和剂量依赖性增加，其方式至少部分涉及PM的铁含量（在用去铁胺预处理的10微克/平方厘米区域快铁颗粒刺激RAW 264.7细胞8小时后，TNF产生受到34%的抑制）。在小鼠体内也短暂观察到类似的细胞因子产生增加，同时伴有支气管肺泡灌洗中性粒细胞细胞数增加（区域快铁处理的小鼠在24小时后多形核中性粒细胞占84.83±0.98%，而载体处理的动物为7.33±0.99%）。地铁PM在体外和体内均诱导MMP - 12和HO - 1表达增加。巴黎地铁系统的PM具有短暂的生物学效应。需要进一步研究以更好地理解这些发现的病理生理学意义。
