Mantecca Paride, Sancini Giulio, Moschini Elisa, Farina Francesca, Gualtieri Maurizio, Rohr Annette, Miserocchi Giuseppe, Palestini Paola, Camatini Marina
Department of Environmental Sciences, POLARIS Research Center, University of Milano-Bicocca, 1 piazza della Scienza, Milan 20126, Italy.
Toxicol Lett. 2009 Sep 28;189(3):206-14. doi: 10.1016/j.toxlet.2009.05.023. Epub 2009 Jun 6.
Tire particles (TP) represent a significant component of urban air pollution (PM), constituting more than 10% of PM10 mass at urban locations with heavy traffic. The purpose of this study was to evaluate the effects of size-fractionated TP in an animal exposure model frequently used to assess the health effects of air pollutants. Potential pro-inflammatory and toxic effects of TP2.5 (<2.5 microm) and TP10 (<10 microm) were investigated through instillation of suspensions of these materials in BALB/c mice. Bronchoalveolar lavage fluid (BALF) was screened for total protein, lactate dehydrogenase (LDH), alkaline phosphatase (AP), and beta-glucuronidase (B-Gluc) as markers of cytotoxicity; glutathione (GSH) and superoxide dismutase (SOD) as markers of oxidative potential; and tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2), and inflammatory cells as markers of inflammation. Concomitantly, histological analysis of TP-exposed lungs was performed. A single intratracheal instillation of 10 microg/100 microl, 100 microg/100 microl or 200 microg/100 microl was performed, and after 24h mice were euthanized and BALF examined. Inflammatory cellular profiles showed dose-dependent responses after TP10 exposure, while strong cytotoxic effects, including increases in total protein, LDH and AP, were observed to be associated to TP2.5 exposure. Histologically, TP10-treated lungs mainly showed inflammatory tissue infiltration, in contrast to TP2.5-treated lungs, where lysis of the alveolar barrier appeared to be the most characteristic lesion. Our biochemical, cytological, and histological results indicated differential lung toxicity mechanisms elicited by size-fractionated TP, in agreement with other studies performed in in vivo systems that have shown that lung responses to inhaled or instilled particles are affected by particle size. We conclude that lung toxicity induced by TP10 was primarily due to macrophage-mediated inflammatory events, while toxicity induced by TP2.5 appeared to be related more closely to cytotoxicity.
轮胎颗粒（TP）是城市空气污染（PM）的重要组成部分，在交通繁忙的城市地区，其在PM10质量中所占比例超过10%。本研究的目的是在常用于评估空气污染物健康影响的动物暴露模型中，评估不同粒径的TP的影响。通过将这些物质的悬浮液滴入BALB/c小鼠体内，研究了TP2.5（<2.5微米）和TP10（<10微米）潜在的促炎和毒性作用。对支气管肺泡灌洗液（BALF）进行检测，以总蛋白、乳酸脱氢酶（LDH）、碱性磷酸酶（AP）和β-葡萄糖醛酸酶（B-Gluc）作为细胞毒性标志物；以谷胱甘肽（GSH）和超氧化物歧化酶（SOD）作为氧化潜能标志物；以肿瘤坏死因子-α（TNF-α）、巨噬细胞炎性蛋白-2（MIP-2）和炎性细胞作为炎症标志物。同时，对暴露于TP的肺部进行组织学分析。进行单次气管内滴注，剂量分别为10微克/100微升、100微克/100微升或200微克/100微升，24小时后对小鼠实施安乐死并检查BALF。炎性细胞谱显示TP10暴露后呈剂量依赖性反应，而观察到TP2.5暴露与包括总蛋白、LDH和AP升高在内的强烈细胞毒性作用有关。组织学上，TP10处理的肺部主要表现为炎性组织浸润，与之形成对比的是，TP2.5处理的肺部，肺泡屏障溶解似乎是最具特征性的病变。我们的生化、细胞学和组织学结果表明，不同粒径的TP引发了不同的肺毒性机制，这与在体内系统中进行的其他研究一致，这些研究表明，肺部对吸入或滴注颗粒的反应受颗粒大小影响。我们得出结论，TP10诱导的肺毒性主要归因于巨噬细胞介导的炎性事件，而TP2.5诱导的毒性似乎与细胞毒性关系更为密切。
