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.
Conclusion
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.
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.
Conclusion
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.
| Original language | English |
|---|---|
| Article number | 0138762 |
| Number of pages | 15 |
| Journal | PloS ONE |
| Volume | 10 |
| Issue number | 9 |
| Early online date | 25 Sept 2015 |
| DOIs | |
| Publication status | Published - 25 Sept 2015 |
Bibliographical note
This work was funded and supported by a Wellcome Trust grant 086756/B/08/Z (JR); a Wellcome Trust Project Grant 083606/A/07/Z (RSH); and Malawi-Liverpool-Wellcome Trust Clinical Research Programme 084679/Z/08/Z (RSH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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- Chronic Household Air Pollution Exposure Is Associated with Impaired Alveolar Macrophage Function in Malawian NonSmokers
Copyright: © 2015 Rylance et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. https://creativecommons.org/licenses/by/4.0/
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Data from: Chronic household air pollution exposure is associated with impaired alveolar macrophage function in Malawian non-smokers
Rylance, J. (Creator), Chimpini, C. (Creator), Semple, S. (Creator), Russell, D. G. (Creator), Jackson, M. J. (Creator), Heyderman, R. S. (Creator), Gordon, S. B. (Creator) & Lee, A. (Data Manager), Dryad Digital Repository, 25 Sept 2016
DOI: 10.5061/dryad.89nj3
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