Baulig Augustin, Singh Seema, Marchand Alexandre, Schins Roel, Barouki Robert, Garlatti Michèle, Marano Francelyne, Baeza-Squiban Armelle
Univ Paris Diderot-Paris 7, Unit of Functional and Adaptive Biology (BFA) EAC CNRS 7059, Laboratory of Molecular and Cellular Responses to Xenobiotics, 5 rue Thomas Mann, Case 7073, 75205 Paris Cedex 13, France.
Toxicology. 2009 Jul 10;261(3):126-35. doi: 10.1016/j.tox.2009.05.007. Epub 2009 May 19.
Particulate matter (PM) is suspected to play a role in environmentally-induced pathologies. Due to its complex composition, the contribution of each PM components to PM-induced biological effects remains unclear. Four samples of Paris PM(2.5) having different polyaromatic hydrocarbons and metals contents were compared with each other and with their respective aqueous and organic extracts used alone or in combination. The four PM(2.5) samples similarly induced granulocyte macrophage-colony stimulating factor (GM-CSF) release, a pro-inflammatory cytokine, by human bronchial epithelial cells. It results from the activation of upstream signalling pathways and the modulation of the cellular redox state that is different according to PM(2.5) samples. The PM-aqueous extracts contained soluble metals involved in hydroxyl radical production in abiotic conditions. However they slightly contributed to the intracellular reactive oxygen species production and GM-CSF release by comparison with organic extracts. Organic compounds transactivated the xenobiotic responsive element (XRE) and antioxidant responsive element (ARE), leading to increased cytochrome P450 1A1 expression and NADPH-quinone oxydoreductase-1 expression respectively but to different extend according to PM samples underlying differences in their bioavailability. Our study underlines that chemical composition of particles per se is insufficient to predict cellular effects and that the interaction and the bioavailability of the various components were critical.
颗粒物（PM）被怀疑在环境诱导的病理学中起作用。由于其成分复杂，每种PM成分对PM诱导的生物学效应的贡献仍不清楚。将四个具有不同多环芳烃和金属含量的巴黎PM2.5样本相互比较，并与单独或组合使用的各自的水提取物和有机提取物进行比较。四个PM2.5样本同样诱导人支气管上皮细胞释放粒细胞巨噬细胞集落刺激因子（GM-CSF），一种促炎细胞因子。这是由上游信号通路的激活和细胞氧化还原状态的调节导致的，而细胞氧化还原状态根据PM2.5样本的不同而不同。PM水提取物含有在非生物条件下参与羟基自由基产生的可溶性金属。然而，与有机提取物相比，它们对细胞内活性氧的产生和GM-CSF的释放贡献较小。有机化合物反式激活了外源性反应元件（XRE）和抗氧化反应元件（ARE），分别导致细胞色素P450 1A1表达和NADPH-醌氧化还原酶-1表达增加，但根据PM样本生物利用度的差异，增加的程度不同。我们的研究强调，颗粒本身的化学成分不足以预测细胞效应，各种成分的相互作用和生物利用度至关重要。
