title: Low-Dose Oxygen Enhances Macrophage-Derived Bacterial Clearance following Cigarette Smoke Exposure.
abstract: Background. Chronic obstructive pulmonary disease (COPD) is a common, smoking-related lung disease. Patients with COPD frequently suffer disease exacerbations induced by bacterial respiratory infections, suggestive of impaired innate immunity. Low-dose oxygen is a mainstay of therapy during COPD exacerbations; yet we understand little about whether oxygen can modulate the effects of cigarette smoke on lung immunity. Methods. Wild-type mice were exposed to cigarette smoke for 5 weeks, followed by intratracheal instillation of Pseudomonas aeruginosa (PAO1) and 21% or 35-40% oxygen. After two days, lungs were harvested for PAO1 CFUs, and bronchoalveolar fluid was sampled for inflammatory markers. In culture, macrophages were exposed to cigarette smoke and oxygen (40%) for 24 hours and then incubated with PAO1, followed by quantification of bacterial phagocytosis and inflammatory markers. Results. Mice exposed to 35-40% oxygen after cigarette smoke and PAO1 had improved survival and reduced lung CFUs and inflammation. Macrophages from these mice expressed less TNF-α and more scavenger receptors. In culture, macrophages exposed to cigarette smoke and oxygen also demonstrated decreased TNF-α secretion and enhanced phagocytosis of PAO1 bacteria. Conclusions. Our findings demonstrate a novel, protective role for low-dose oxygen following cigarette smoke and bacteria exposure that may be mediated by enhanced macrophage phagocytosis.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Bain
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Tripathi
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Pooja
authors.initials: P
authors.lastname: Mandke
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Gans
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Franco R
authors.initials: FR
authors.lastname: D'Alessio
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Venkataramana K
authors.initials: VK
authors.lastname: Sidhaye
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Neil R
authors.initials: NR
authors.lastname: Aggarwal
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D016130:Immunophenotyping; D018836:Inflammation Mediators; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D010100:Oxygen / Q000008:administration & dosage*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012906:Smoke; D010100:Oxygen