Gene expression induction of volatile organic compound and/or polycyclic aromatic hydrocarbon-metabolizing enzymes in isolated human alveolar macrophages in response to airborne particulate matter (PM

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• 作者：Franç ; oise Saint-Georges ; Imane Abbas ; Sylvain Billet ; Anthony Verdin ; Pierre Gosset ; Philippe Mulliez ; Pirouz Shirali ; Guillaume Garç ; on
• 关键词：Healthy outpatients ; Bronchoalveolar lavage ; Alveolar macrophage ; Particulate matter ; Cytotoxicity ; Metabolic activation ; Volatile organic compounds ; Polycyclic aromatic hydrocarbons
• 刊名：Toxicology
• 出版年：2008
• 出版时间：28 February 2008
• 年：2008
• 卷：244
• 期：2-3
• 页码：220-230
• 全文大小：399 K

文摘

To contribute to improve the knowledge of the underlying mechanisms of action involved in air pollution particulate matter (PM)-induced cytotoxicity, we were interested in the metabolic activation of volatile organic compounds (VOC) and/or polycyclic aromatic hydrocarbons (PAH) coated onto Dunkerque City's PM_2.5 in human alveolar macrophages (AM) isolated from bronchoalveolar lavage fluid (BALF). This in vitro cell lung model is closer to the normal in vivo situation than other lung cell lines, notably in the characteristics that AM display in terms of gene expression of phase I and phase II-metabolizing enzymes. The bronchoscopic examinations and BAL procedures were carried out without any complications. After 24, 48 and 72 h of incubation, calculated lethal concentrations at 10 % and 50 % of collected airborne PM were 14.93 μg PM/mL and 74.63 μg PM/mL, respectively, and indicated the higher sensibility of such target lung cells. Moreover, VOC and/or PAH coated onto PM induced gene expression of cytochrome P450 (cyp) 1a1, cyp2e1, nadph quinone oxydo-reductase-1, and glutathione S-transferase-pi 1 and mu 3, versus controls, suggesting thereby the formation of biologically reactive metabolites. In addition, these results suggested the role of physical carrier of carbonaceous core of PM, which can, therefore, increase both the penetration and the retention of attached-VOC into the cells, thereby enabling them to exert a longer induction. Hence, we concluded that the metabolic activation of the very low doses of VOC and/or PAH coated onto Dunkerque City's PM_2.5 is one of the underlying mechanisms of action closely involved in its cytotoxicity in isolated human AM in culture.