title: Chronic Household Air Pollution Exposure Is Associated with Impaired Alveolar Macrophage Function in Malawian Non-Smokers.
abstract: BACKGROUND
  Household air pollution in low income countries is an important cause of mortality from respiratory infection. We hypothesised that chronic smoke exposure is detrimental to alveolar macrophage function, causing failure of innate immunity. We report the relationship between macrophage function and prior smoke exposure in healthy Malawians.
  
  
  METHODS
  Healthy subjects exposed daily to cooking smoke at home volunteered for bronchoalveolar lavage. Alveolar macrophage particulate content was measured as a known correlate of smoke exposure. Phagocytosis and intraphagosomal function (oxidative burst and proteolysis) were measured by a flow cytometric assay. Cytokine responses in macrophages were compared following re-exposure in vitro to wood smoke, before and after glutathione depletion.
  
  
  RESULTS
  Volunteers had a range of alveolar macrophage particulate loading. The macrophage capacity for phagosomal oxidative burst was negatively associated with alveolar macrophage particulate content (n = 29, r2 = 0.16, p = 0.033), but phagocytosis per se and proteolytic function were unaffected. High particulate content was associated with lower baseline CXCL8 release (ratio 0.51, CI 0.29-0.89) and lower final concentrations on re-exposure to smoke in vitro (ratio 0.58, CI 0.34-0.97). Glutathione depletion augmented CXCL8 responses by 1.49x (CI 1.02-2.17) compared with wood smoke alone. This response was specific to smoke as macrophages response to LPS were not modulated by glutathione.
  
  
  CONCLUSIONS
  Chronic smoke exposure is associated with reduced human macrophage oxidative burst, and dampened inflammatory cytokine responses. These are critical processes in lung defence against infection and likely to underpin the relationship between air pollution and pneumonia.
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Dept of Respiratory Medicine, Clinical Sciences Centre, University Hospital Aintree, Liverpool, United Kingdom; Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rylance
authors.affiliation: Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi.
authors.forename: Chikondi
authors.initials: C
authors.lastname: Chimpini
authors.affiliation: Scottish Centre for Indoor Air, Division of Applied Health Sciences, University of Aberdeen, United Kingdom.
authors.forename: Sean
authors.initials: S
authors.lastname: Semple
authors.affiliation: Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: David G
authors.initials: DG
authors.lastname: Russell
authors.affiliation: Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Jackson
authors.affiliation: Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Dept of Respiratory Medicine, Clinical Sciences Centre, University Hospital Aintree, Liverpool, United Kingdom; Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gordon
mesh_terms: D000328:Adult; D016902:Air Pollution, Indoor / Q000009:adverse effects*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D016209:Interleukin-8 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000502:physiology*; D008295:Malawi; D008297:Male; D018384:Oxidative Stress; D010587:Phagocytosis; D012906:Smoke / Q000009:adverse effects*; D055815:Young Adult
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D012906:Smoke; D005978:Glutathione