Chronic Household Air Pollution Exposure Is Associated with Impaired Alveolar Macrophage Function in Malawian Non-Smokers

Jamie Rylance, Chikondi Chimpini, Sean Semple, David G Russell, Malcolm J. Jackson, Robert S. Heyderman, Stephen B Gordon

Research output: Contribution to journalArticle

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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.
Original languageEnglish
Article number0138762
Number of pages15
JournalPloS ONE
Volume10
Issue number9
Early online date25 Sep 2015
DOIs
Publication statusPublished - 25 Sep 2015

Fingerprint

Air Pollution
Alveolar Macrophages
air pollution
smoke
Air pollution
Smoke
households
macrophages
Macrophages
Respiratory Burst
particulates
Glutathione
glutathione
phagocytosis
Phagocytosis
Wood
cytokines
Proteolysis
Cytokines
Cooking

Cite this

Rylance, J., Chimpini, C., Semple, S., Russell, D. G., Jackson, M. J., Heyderman, R. S., & Gordon, S. B. (2015). Chronic Household Air Pollution Exposure Is Associated with Impaired Alveolar Macrophage Function in Malawian Non-Smokers. PloS ONE, 10(9), [0138762]. https://doi.org/10.1371/journal.pone.0138762

Chronic Household Air Pollution Exposure Is Associated with Impaired Alveolar Macrophage Function in Malawian Non-Smokers. / Rylance, Jamie; Chimpini, Chikondi; Semple, Sean; Russell, David G; Jackson, Malcolm J.; Heyderman, Robert S.; Gordon, Stephen B.

In: PloS ONE, Vol. 10, No. 9, 0138762, 25.09.2015.

Research output: Contribution to journalArticle

Rylance, J, Chimpini, C, Semple, S, Russell, DG, Jackson, MJ, Heyderman, RS & Gordon, SB 2015, 'Chronic Household Air Pollution Exposure Is Associated with Impaired Alveolar Macrophage Function in Malawian Non-Smokers' PloS ONE, vol. 10, no. 9, 0138762. https://doi.org/10.1371/journal.pone.0138762
Rylance, Jamie ; Chimpini, Chikondi ; Semple, Sean ; Russell, David G ; Jackson, Malcolm J. ; Heyderman, Robert S. ; Gordon, Stephen B. / Chronic Household Air Pollution Exposure Is Associated with Impaired Alveolar Macrophage Function in Malawian Non-Smokers. In: PloS ONE. 2015 ; Vol. 10, No. 9.
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abstract = "BackgroundHousehold 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.MethodsHealthy 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.ResultsVolunteers 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.ConclusionChronic 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.",
author = "Jamie Rylance and Chikondi Chimpini and Sean Semple and Russell, {David G} and Jackson, {Malcolm J.} and Heyderman, {Robert S.} and Gordon, {Stephen B}",
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AU - Russell, David G

AU - Jackson, Malcolm J.

AU - Heyderman, Robert S.

AU - Gordon, Stephen B

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N2 - BackgroundHousehold 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.MethodsHealthy 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.ResultsVolunteers 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.ConclusionChronic 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.

AB - BackgroundHousehold 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.MethodsHealthy 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.ResultsVolunteers 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.ConclusionChronic 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.

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