Milano summer particulate matter (PM10) triggers lung inflammation and extra pulmonary adverse events in mice.
Milano summer particulate matter (PM10) triggers lung inflammation and extra pulmonary adverse events in mice.
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DOI：
10.1371/journal.pone.0056636
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Palestini P
中科院分区：
文献类型：
--
作者：
Farina F;Sancini G;Battaglia C;Tinaglia V;Mantecca P;Camatini M;Palestini P
最近的研究表明，颗粒物（PM）暴露与肺和心血管疾病相关的死亡率和发病率增加之间存在联系;越来越多的证据表明空气污染在中枢神经系统疾病中的新作用。本研究的目的是研究PM10对肺和肺外组织的影响。将Milano PM10 sum经气管内滴注到BALB/c小鼠中。筛选支气管肺泡灌洗液、肺实质、心脏和脑的炎症标志物（细胞计数、细胞因子、ET-1、HO-1、MPO、iNOS）、细胞毒性标志物（LDH、ALP、Hsp 70、Caspase 8-p18、Caspase 3-p17）、推定的促癌标志物（Cyp 1B 1）和TLR 4通路活化。同时检测脑组织中CD 68、TNF-α、GFAP的表达。在血液中，进行细胞计数，同时筛选血浆中的内皮活化（sP-选择素，ET-1）和炎症标志物（TNF-α，MIP-2，IL-1β，MPO）。研究了肺和血液中的基因上调（HMOX 1、Cyp 1B 1、IL-1β、MIP-2、MPO）和miR-21。PM10 sum处理的小鼠的呼吸道中的炎症已经通过增加的PMNs百分比、增加的ET-1、MPO和细胞因子水平在BALf和肺实质中被证实。在PM10 sum处理的小鼠中，肺部炎症的全身扩散与血液总细胞计数和中性粒细胞百分比增加以及血液MPO增加有关。血浆ET-1和sP-选择素的显著升高证实了血-内皮界面激活。此外，PM10 sum诱导心脏内皮细胞活化和多环芳烃代谢，通过增加ET-1和Cyp 1B 1水平证明。此外，PM10 sum引起脑HO-1和ET-1的增加。这些结果表明，炎症介质、超细颗粒、LPS、与PM10 sum相关的金属从肺转移到血流，从而引发全身反应，主要涉及心脏和大脑。我们的研究结果为PM10 sum的毒性提供了额外的见解，并有助于揭示城市空气污染相关疾病发展的机制。
Recent studies have suggested a link between particulate matter (PM) exposure and increased mortality and morbidity associated with pulmonary and cardiovascular diseases; accumulating evidences point to a new role for air pollution in CNS diseases. The purpose of our study is to investigate PM10sum effects on lungs and extra pulmonary tissues. Milano PM10sum has been intratracheally instilled into BALB/c mice. Broncho Alveolar Lavage fluid, lung parenchyma, heart and brain were screened for markers of inflammation (cell counts, cytokines, ET-1, HO-1, MPO, iNOS), cytotoxicity (LDH, ALP, Hsp70, Caspase8-p18, Caspase3-p17) for a putative pro-carcinogenic marker (Cyp1B1) and for TLR4 pathway activation. Brain was also investigated for CD68, TNF-α, GFAP. In blood, cell counts were performed while plasma was screened for endothelial activation (sP-selectin, ET-1) and for inflammation markers (TNF-α, MIP-2, IL-1β, MPO). Genes up-regulation (HMOX1, Cyp1B1, IL-1β, MIP-2, MPO) and miR-21 have been investigated in lungs and blood. Inflammation in the respiratory tract of PM10sum-treated mice has been confirmed in BALf and lung parenchyma by increased PMNs percentage, increased ET-1, MPO and cytokines levels. A systemic spreading of lung inflammation in PM10sum-treated mice has been related to the increased blood total cell count and neutrophils percentage, as well as to increased blood MPO. The blood-endothelium interface activation has been confirmed by significant increases of plasma ET-1 and sP-selectin. Furthermore PM10sum induced heart endothelial activation and PAHs metabolism, proved by increased ET-1 and Cyp1B1 levels. Moreover, PM10sum causes an increase in brain HO-1 and ET-1. These results state the translocation of inflammation mediators, ultrafine particles, LPS, metals associated to PM10sum, from lungs to bloodstream, thus triggering a systemic reaction, mainly involving heart and brain. Our results provided additional insight into the toxicity of PM10sum and could facilitate shedding light on mechanisms underlying the development of urban air pollution related diseases.
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