title: 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 (PM2.5).
abstract: 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 PM2.5 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 72h of incubation, calculated lethal concentrations at 10% and 50% of collected airborne PM were 14.93microg PM/mL and 74.63microg 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 PM2.5 is one of the underlying mechanisms of action closely involved in its cytotoxicity in isolated human AM in culture.
authors.affiliation: Service de Pneumologie, Hôpital Saint-Philibert, Groupement Hospitalier de l'Institut Catholique-Faculté Libre de Médecine de Lille, rue du Grand But, BP 249, 59462 Lomme Cedex, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Saint-Georges
authors.forename: Imane
authors.initials: I
authors.lastname: Abbas
authors.forename: Sylvain
authors.initials: S
authors.lastname: Billet
authors.forename: Anthony
authors.initials: A
authors.lastname: Verdin
authors.forename: Pierre
authors.initials: P
authors.lastname: Gosset
authors.forename: Philippe
authors.initials: P
authors.lastname: Mulliez
authors.forename: Pirouz
authors.initials: P
authors.lastname: Shirali
authors.forename: Guillaume
authors.initials: G
authors.lastname: Garçon
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D001999:Bronchoscopy; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology*; D008855:Microscopy, Electron, Scanning; D009930:Organic Chemicals / Q000378:metabolism*; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism*; D014025:Titanium / Q000633:toxicity
chemical_list: D009930:Organic Chemicals; D052638:Particulate Matter; D011084:Polycyclic Aromatic Hydrocarbons; C009495:titanium dioxide; D003577:Cytochrome P-450 Enzyme System; D014025:Titanium