title: Oxidized phospholipid, 1-palmitoyl-2-(9'-oxo-nonanoyl)-glycerophosphocholine (PON-GPC), produced in the lung due to cigarette smoking, impairs immune function in macrophages.
abstract: BACKGROUND
  Pulmonary innate immunity is impaired in cigarette smokers, because the abundant oxidants present in cigarette smoke (CS) cause injury to lung cells. Pulmonary surfactant is a unique material that is important roles in reducing surface tension in the lung and defending against invading pathogens. Oxidants reportedly cleave surfactant phospholipids, resulting in the production of oxidized phospholipids, such as 1-palmitoyl-2-(9'-oxo-nonanoyl)-glycerophosphocholine (PON-GPC). Although oxidation of surfactant lipids is thought to be involved in the pathogenesis of smoking-related lung disease, there are no reports on the effect of oxidized surfactant lipid on the immune function of macrophages. We hypothesized that cigarette smoking elevates PON-GPC levels in the lung, and that PON-GPC impairs the innate immune function of macrophages.
  
  
  METHODS
  The levels of PON-GPC in bronchoalveolar lavage fluid (BALF) recovered from mice exposed to CS for 2 weeks (n = 7) were measured by liquid chromatography with electrospray-ionization tandem mass spectrometry. The effects of PON-GPC on inducibility of tumor necrosis factor (TNF)-α, nitric oxide (NO), and nicotinamide adenine dinucleotide phosphate (NADP(+)) production, as well as bactericidal activity, were investigated in RAW264.7 cells or primary alveolar macrophages.
  
  
  RESULTS
  The levels of PON-GPC in BALF of mice exposed to CS were significantly elevated, compared with those of control mice. PON-GPC attenuated TNF-α, NO, and NADP(+) production in macrophages on stimulation with LPS plus IFN-γ. PON-GPC treatment attenuated the phosphorylation of p38 mitogen-activated protein kinase (MAPK). In addition, PON-GPC reduced the bactericidal activity of RAW264.7 cells.
  
  
  CONCLUSIONS
  CS may attenuate innate immunity in the lungs through oxidization of surfactant phospholipids.
authors: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors: Tomomi
authors: T
authors: Kimura
authors: Yoko
authors: Y
authors: Shibata
authors: Keiko
authors: K
authors: Yamauchi
authors: Akira
authors: A
authors: Igarashi
authors: Sumito
authors: S
authors: Inoue
authors: Shuichi
authors: S
authors: Abe
authors: Kazuhiro
authors: K
authors: Fujita
authors: Yoichi
authors: Y
authors: Uosaki
authors: Isao
authors: I
authors: Kubota
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D009249:NADP / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D010587:Phagocytosis / Q000187:drug effects; D010713:Phosphatidylcholines / Q000032:analysis / Q000276:immunology* / Q000494:pharmacology*; D010743:Phospholipids / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects / Q000276:immunology*; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: C097369:1-palmitoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphocholine; D008070:Lipopolysaccharides; D010713:Phosphatidylcholines; D010743:Phospholipids; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D015060:1,2-Dipalmitoylphosphatidylcholine; D009569:Nitric Oxide; D009249:NADP; D007371:Interferon-gamma; D048051:p38 Mitogen-Activated Protein Kinases