Influences of ozone exposure upon macrophage responsivity to N-formyl-methionyl-leucyl-phenylalanine: mobility and metabolic changes.
Alveolar macrophages represent one of the first lines of cell defence in the lungs. They employ several mechanisms, including phagocytosis and secretion of reactive oxygen and nitrogen species. fMLP, a formylated peptide of bacterial origin, is a potent inducer of phagocyte chemotaxis and is also involved in generating antimicrobial agents such as nitric oxide (NO) and hydrogen peroxide (H2O2). In this study we analysed the in vitro effects of fMLP on the mobility of the THP-1 cell line, which served as a model for alveolar macrophages. Cell mobility and cytotoxicity were also analysed after pre-exposures to an atmosphere polluted with ozone (0.03-0.5 ppm) followed by a fMLP treatment. Finally, the secreted molecules (H2O2 and NO) were measured after ozone exposures ranging from 5 to 30 min and fMLP action. Activation by fMLP alone induced cell movement, whereas pre-exposure to the ozone concentrations decreased it. Addition of fMLP had different effects on cytotoxicity, mobility and metabolite secretion by the cells: (1) cytotoxicity increased depending on ozone concentrations and exposure times; (2) during the first 5 min and for all ozone concentrations, an average decrease of 50% of activated cell mobility was observed; (3) H2O2 was increased, even in combination with ozone; (4) NO was detected at 731 nM, a result that was not affected by ozone pre-exposure.
Klestadt
Deborah
D
IUT de Thionville-Yutz, Laboratoire, d'Immunologie-Microbiologie (ESE-CNRS, unité FRE2635), 1, Impasse A. Kastler, F-57970 Yutz, France. dklestad@ulb.ac.be
Laval-Gilly
Philippe
P
Foucaud
Laurent
L
Falla
Jaïro
J
D000393:Air Pollutants / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D013997:Time Factors
D000393:Air Pollutants; D004338:Drug Combinations; D010083:Oxidants, Photochemical; D009569:Nitric Oxide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010126:Ozone; D006861:Hydrogen Peroxide