title: Tissue injury following inhalation of fine particulate matter and hydrogen peroxide is associated with altered production of inflammatory mediators and antioxidants by alveolar macrophages.
abstract: Hydrogen peroxide (H(2)O(2)) is present in the atmosphere at concentrations known to induce cell and tissue damage. However, inhaled H(2)O(2) vapor should not reach the lower lung due to its high water solubility. It has been suggested that hygroscopic components of particulate matter (PM) may transport H(2)O(2) into the lower lung and induce tissue injury and this was investigated. Ammonium sulfate [(NH(4))(2)SO(4)] was selected as a model for fine atmospheric PM. Treatment of female Sprague-Dawley rats with (NH(4))(2)SO(4) (429 or 215 microg/m(3); 0.3-0.4 microm mass median diameter) or H(2)O(2) (10, 20, or 100 ppb) alone or in combination for 2 h had no major effect on bronchoalveolar lavage fluid cell number or viability or on protein content or lactate dehydrogenase levels, either immediately or 24 h after exposure, relative to air-exposed rats. However, electron microscopy revealed increased numbers of neutrophils in pulmonary capillaries adhered to the vascular endothelium in rats treated with the combination of (NH(4))(2)SO(4) + H(2)O(2). Exposure of rats to (NH(4))(2)SO(4) + H(2)O(2) also resulted in tumor necrosis factor-alpha (TNF-alpha) production by alveolar macrophages. This was observed immediately and 24 h after exposure. Immediately after inhalation of (NH(4))(2)SO(4) + H(2)O(2), a transient increase in production of superoxide anion by alveolar macrophages was observed. In contrast, nitric oxide production by cells from rats exposed to (NH(4))(2)SO(4) + H(2)O(2) or H(2)O(2) alone was decreased, and this persisted for 24 h. Decreases in nitric oxide may be due to superoxide anion-driven formation of peroxynitrite. In this regard, nitrotyrosine, an in vivo marker of peroxynitrite, was detected in lung tissue after exposure of rats to (NH(4))(2)SO(4) + H(2)O(2) or H(2)O(2). We also found that expression of the antioxidant enzyme heme oxygenase-1 by stimulated alveolar macrophages was increased following exposure of rats to (NH(4))(2)SO(4) + H(2)O(2). Taken together, these studies demonstrate that the biological effects of inhaled fine PM are augmented by H(2)O(2). Moreover, tissue injury induced by fine PM may be related to altered production of cytotoxic mediators by alveolar macrophages.
authors.affiliation: Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Morio
authors.forename: K A
authors.initials: KA
authors.lastname: Hooper
authors.forename: J
authors.initials: J
authors.lastname: Brittingham
authors.forename: T H
authors.initials: TH
authors.lastname: Li
authors.forename: R E
authors.initials: RE
authors.lastname: Gordon
authors.forename: B J
authors.initials: BJ
authors.lastname: Turpin
authors.forename: D L
authors.initials: DL
authors.lastname: Laskin
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage / Q000633:toxicity*; D000645:Ammonium Sulfate / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D051546:Cyclooxygenase 2; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000008:administration & dosage / Q000633:toxicity; D018836:Inflammation Mediators / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010316:Particle Size; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012140:Respiratory Tract Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000336:Aerosols; D000975:Antioxidants; D006360:Heat-Shock Proteins; D018836:Inflammation Mediators; D007527:Isoenzymes; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000645:Ammonium Sulfate