title: Carbon in airway macrophages from children with asthma.
abstract: BACKGROUND
  Airway macrophage (AM) phagocytosis is impaired in severe asthma. Prostaglandin (PG) E2 and D2 are increased in severe asthma and suppress AM phagocytic function in vitro. In this study, we sought evidence for PG-mediated impairment of phagocytosis of inhalable carbonaceous particulate matter (PM) by AM in children with severe asthma compared with mild asthmatics and healthy controls.
  
  
  METHODS
  AM were obtained from children with asthma and healthy controls using induced sputum. AM carbon area (μm(2)) was assessed by image analysis. In a subgroup of asthmatics, urinary PGE2 and PGD2 metabolites were measured by high-performance liquid chromatography, and PM exposure at the home address was modelled. Phagocytosis of PM by human monocyte-derived macrophages and rat AM was assessed in vitro by image analysis.
  
  
  RESULTS
  AM carbon was 51% lower in children with moderate-to-severe asthma (n=36) compared with mild asthmatics (n=12, p<0.01) and healthy controls (n=47, p<0.01). There was no association between modelled PM exposure and AM carbon in 33 asthmatics who had a urine sample, but there was an inverse association between AM carbon and urinary metabolites of PGE2 and D2 (n=33, rs=-0.40, p<0.05, and rs=-0.44, p<0.01). PGE2 10(-6) M, but not PGD2 10(-6) M, suppressed phagocytosis of PM10 by human macrophages in vitro (p<0.05 vs control). PGE2 10(-6) M also suppressed phagocytosis of PM10 by rat AM in vitro (p<0.01 vs control).
  
  
  CONCLUSIONS
  Phagocytosis of inhaled carbonaceous PM by AMs is impaired in severe asthma. PGE2 may contribute to impaired AM phagocytic function in severe asthma.
authors.affiliation: Blizard Institute, Queen Mary, University of London, London, UK.
authors.forename: Rossa E
authors.initials: RE
authors.lastname: Brugha
authors.affiliation: Blizard Institute, Queen Mary, University of London, London, UK.
authors.forename: Naseem
authors.initials: N
authors.lastname: Mushtaq
authors.affiliation: Blizard Institute, Queen Mary, University of London, London, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Round
authors.affiliation: Blizard Institute, Queen Mary, University of London, London, UK.
authors.forename: Dev H
authors.initials: DH
authors.lastname: Gadhvi
authors.affiliation: Blizard Institute, Queen Mary, University of London, London, UK.
authors.forename: Isobel
authors.initials: I
authors.lastname: Dundas
authors.affiliation: Department of Infection, Immunity and Inflammation, University Hospitals of Leicester, Leicester, UK.
authors.forename: Erol
authors.initials: E
authors.lastname: Gaillard
authors.affiliation: Blizard Institute, Queen Mary, University of London, London, UK.
authors.forename: Lee
authors.initials: L
authors.lastname: Koh
authors.affiliation: Department of Respiratory Paediatrics, Imperial College, London, UK.
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Fleming
authors.affiliation: Department of Social and Environmental Health Research, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lewis
authors.affiliation: Department of Medicine, Jagiellonian University Medical School, Krakow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Sanak
authors.affiliation: MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, King's College London, UK.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Wood
authors.affiliation: MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, King's College London, UK.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Barratt
authors.affiliation: MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, King's College London, UK.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Mudway
authors.affiliation: MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, King's College London, UK.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Kelly
authors.affiliation: Blizard Institute, Queen Mary, University of London, London, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Griffiths
authors.affiliation: Blizard Institute, Queen Mary, University of London, London, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Grigg
mesh_terms: D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D002244:Carbon / Q000032:analysis* / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002851:Chromatography, High Pressure Liquid; D015232:Dinoprostone / Q000276:immunology / Q000502:physiology / Q000652:urine; D004781:Environmental Exposure / Q000032:analysis*; D005260:Female; D006801:Humans; D008131:London; D008264:Macrophages / Q000737:chemistry* / Q000276:immunology; D008297:Male; D010316:Particle Size; D010587:Phagocytosis / Q000276:immunology / Q000502:physiology*; D015230:Prostaglandin D2 / Q000276:immunology / Q000502:physiology / Q000652:urine; D013147:Spirometry; D013183:Sputum / Q000737:chemistry* / Q000276:immunology; D014505:Urban Population
chemical_list: D002244:Carbon; D015232:Dinoprostone; D015230:Prostaglandin D2
keywords: Macrophage Biology