title: Soluble metals in residual oil fly ash alter innate and adaptive pulmonary immune responses to bacterial infection in rats.
abstract: The soluble metals of the pollutant, residual oil fly ash (ROFA), have been shown to alter pulmonary bacterial clearance in rats. The goal of this study was to determine the potential effects on both the innate and adaptive lung immune responses after bacterial infection in rats pre-exposed to the soluble metals in ROFA. Sprague-Dawley rats were intratracheally dosed (i.t.) at day 0 with ROFA (R-Total) (1.0 mg/100 g body weight), the soluble fraction of ROFA (R-Soluble), the soluble sample subject to a chelator (R-Chelex), or phosphate-buffered saline (Saline). On day 3, rats were administered an i.t. dose of 5 x 10(4)Listeria monocytogenes. On days 6, 8, and 10, bacterial pulmonary clearance was monitored and bronchoalveolar lavage (BAL) was performed on days 3 (pre-infection), 6, 8, and 10. A concentrated first fraction of lavage fluid was retained for analysis of lactate dehydrogenase and albumin to assess lung injury. BAL cell number, phenotype, and production of reactive oxygen (ROS) and nitrogen species (RNS) were assessed, and a variety of cytokines were measured in the BAL fluid. Rats pre-treated with R-Soluble showed elevated lung injury/cytotoxicity and increased cellular influx into the lungs. R-Soluble-treatment also altered ROS, RNS, and cytokine levels, and caused a degree of macrophage and T cell inhibition. These effects of R-Soluble result in increased pulmonary bacterial burden after infection. The results suggest that soluble metals in ROFA increase lung injury and inflammation, and alter both innate and adaptive pulmonary immune responses.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. jur6@cdc.gov
authors.forename: Jenny R
authors.initials: JR
authors.lastname: Roberts
authors.forename: Shih-Houng
authors.initials: SH
authors.lastname: Young
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.forename: James M
authors.initials: JM
authors.lastname: Antonini
mesh_terms: D000222:Adaptation, Physiological; D000393:Air Pollutants / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D002244:Carbon / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*; D060729:Coal Ash; D016207:Cytokines / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007111:Immunity, Cellular / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects*; D008088:Listeriosis / Q000276:immunology*; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008171:Lung Diseases / Q000276:immunology; D008297:Male; D008670:Metals / Q000737:chemistry / Q000633:toxicity; D052638:Particulate Matter / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species / Q000276:immunology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D012995:Solubility
chemical_list: D000393:Air Pollutants; D060729:Coal Ash; D016207:Cytokines; D008670:Metals; D052638:Particulate Matter; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D002244:Carbon