title: Incinerator fly ash provokes alteration of redox equilibrium and liberation of arachidonic acid in vitro.
abstract: Numerous epidemiological studies have associated exposure to ambient particulate matter (PM) with pulmonary and cardiovascular health effects. Macrophages as a part of the primary pulmonary defence system play a crucial role by generating pro- and anti-inflammatory mediators. The aim of the present study was to examine the effect of incinerator fly ash (MAF02) as a model of environmental particulate matter on the formation of reactive oxygen species (ROS) and their ability to induce oxidative stress in RAW264.7 macrophages. Furthermore, the liberation of arachidonic acid (AA) was observed. The interaction of MAF02 with macrophages caused increased mobilisation of AA, accompanied by enhanced expression of cyclooxygenase-2 (COX-2). The MAF02-induced AA liberation was found to depend on an increased intracellular calcium concentration. In addition, MAF02-induced liberation of AA was selectively blocked by an ERK1/2 pathway-specific inhibitor, while inhibition of the p38 MAPK activity had no effect. Fly ash was also observed to induce an increase in cellular glutathione (GSH) content and antioxidative enzyme haem oxygenase-1 (HO-1). In correlation, experiments with dichlorofluorescein demonstrated increased formation of ROS upon treatment with fly ash. In summary, incinerator fly ash induces oxidative stress to a certain extent, resulting in the onset of important mechanisms related to inflammation.
authors.affiliation: 1. Forschungszentrum Karlsruhe, Institut für Toxikologie und Genetik, Abteilung für Molekulare Umwelttoxikologie, Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Fritsch
authors.forename: Silvia
authors.initials: S
authors.lastname: Diabaté
authors.forename: Harald F
authors.initials: HF
authors.lastname: Krug
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism*; D002244:Carbon / Q000494:pharmacology / Q000633:toxicity*; D002460:Cell Line; D060729:Coal Ash; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D017745:Incineration; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D052638:Particulate Matter / Q000494:pharmacology / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D060729:Coal Ash; D052638:Particulate Matter; D017382:Reactive Oxygen Species; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D016718:Arachidonic Acid; D004533:Egtazic Acid; D002244:Carbon; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D005978:Glutathione