title: Second-hand smoke increases nitric oxide and alters the IgE response in a murine model of allergic aspergillosis.
abstract: This study was performed to determine the effects of environmental tobacco smoke (ETS) on nitric oxide (NO) and immunoglobulin (Ig) production in a murine model of allergic bronchopulmonary aspergillosis (ABPA). Adult BALB/c mice were exposed to aged and diluted sidestream cigarette smoke from day 0 through day 43 to simulate "second-hand smoke". During exposure, mice were sensitized to soluble Aspergillus fumigatus (Af) antigen intranasally between day 14 and 24. All Af sensitized mice in ambient air (Af + AIR) made elevated levels of IgE, IgG1, IgM, IgG2a and IgA. Af sensitized mice housed in ETS (Af + ETS) made similar levels of immunoglobulins except for IgE that was significantly reduced in the serum and bronchoalveolar lavage (BAL). However, immunohistochemical evaluation of the lung revealed a marked accumulation of IgE positive cells in the lung parenchyma of these Af + ETS mice. LPS stimulation of BAL cells revealed elevated levels of NO in the Af + AIR group, which was further enhanced in the Af + ETS group. In vitro restimulation of the BAL cells on day 45 showed a THO response with elevated levels of IL3, 4, 5, 10 and IFN-gamma. However, by day 28 the response shifted such that TH2 cytokines increased while IFN-gamma decreased. The Af + ETS group showed markedly reduced levels in all cytokines tested, including the inflammatory cytokine IL6, when compared to the Af + AIR group. These results demonstrate that ETS affects ABPA by further enhancing the NO production and reduces the TH2 and the inflammatory cytokines while altering the pattern of IgE responses.
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Brian W P
authors.initials: BW
authors.lastname: Seymour
authors.forename: Janice L
authors.initials: JL
authors.lastname: Peake
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
authors.forename: Viswanath P
authors.initials: VP
authors.lastname: Kurup
authors.forename: Laurel J
authors.initials: LJ
authors.lastname: Gershwin
mesh_terms: D000818:Animals; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000097:blood / Q000276:immunology* / Q000473:pathology; D001232:Aspergillus fumigatus / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D014028:Tobacco Smoke Pollution
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D015850:Interleukin-6; D014028:Tobacco Smoke Pollution; D009569:Nitric Oxide; D007073:Immunoglobulin E