Department of Experimental Medicine, POLARIS Research Center, University of Milano-Bicocca, 48 via Cadore, Monza 20052, Italy.
Toxicol Lett. 2011 May 10;202(3):209-17. doi: 10.1016/j.toxlet.2011.01.031. Epub 2011 Mar 1.
The toxicity of size-fractionated particulate matter (PM10 and PM2.5) collected in Milano during two different seasons (summer and winter) has been evaluated in vivo. The focus is on time related (3 h, 24 h and 1 week) lung response following a single intratracheal aerosolization in BALB/c mice. The bronchoalveolar lavage fluid (BALf) and the lung parenchyma were screened for different markers of inflammation and cytotoxicity. Histology and immunohistochemistry were performed on excised fixed lungs to assess the effects produced by the different PM fractions. All the analyzed inflammatory markers (PMNs percentage, TNF-α, Hsp70 in the BALf, HO-1 in lung parenchyma), increased after summer PM10 administration; on the contrary winter PM10 and PM2.5 specifically increased the amount of the Cyp1B1, a protein putatively involved in the induction of pro-carcinogenic effect. Moreover, we detected an intensification of LDH activity in the BALf after the administration of winter PM10 and PM2.5, potentially related to an in progress necrotic process while after summer PM10 and PM2.5 administration, the initiation of the caspase cascade suggested a cytotoxic effect sustained by apoptosis. Our results evidenced the toxicity mechanisms elicited by size fractionated PM samples, collected in winter and summer seasons, which differs for dimensions, chemical and microbiological composition. PM10 has been indicated to elicit above all a pro-inflammatory response, linked to its specific biological components, while PM2.5 is supposed to be more harmful due to its smaller dimension and the ability to distribute into the lung alveolar districts. We hypothesized that adverse health effects observed after a single dose of winter PM2.5 is at least partly caused by specific winter PM components, i.e. PAH and transitional metals.
在两个不同季节（夏季和冬季）收集的米兰的分形颗粒物（PM10 和 PM2.5）的毒性已在体内进行了评估。重点是在单次气管内气溶胶化后，观察 BALB/c 小鼠的时间相关（3 h、24 h 和 1 周）肺部反应。支气管肺泡灌洗液（BALf）和肺实质中筛选了不同的炎症和细胞毒性标志物。对切除的固定肺进行组织学和免疫组织化学检查，以评估不同 PM 分数产生的影响。所有分析的炎症标志物（BALf 中的 PMNs 百分比、TNF-α、Hsp70、肺实质中的 HO-1）在夏季 PM10 给药后均增加；相反，冬季 PM10 和 PM2.5 特异性增加了 Cyp1B1 的数量，Cyp1B1 是一种潜在参与诱导前致癌作用的蛋白质。此外，我们在冬季 PM10 和 PM2.5 给药后检测到 BALf 中 LDH 活性增加，可能与正在进行的坏死过程有关，而在夏季 PM10 和 PM2.5 给药后，caspase 级联的启动表明了细胞毒性作用，由细胞凋亡维持。我们的结果证明了冬季和夏季采集的分形 PM 样品引发的毒性机制不同，这与它们的尺寸、化学成分和微生物组成有关。PM10 主要引发炎症反应，这与其特定的生物成分有关，而 PM2.5 由于其较小的尺寸和向肺肺泡区分布的能力而被认为更有害。我们假设单次冬季 PM2.5 剂量后观察到的不良健康影响至少部分是由冬季 PM 的特定成分引起的，即多环芳烃和过渡金属。
