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Authors:
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Rylance J, Fullerton DG, Scriven J, Aljurayyan AN, Mzinza D, Barrett S, Wright AK, Wootton DG, Glennie SJ, Baple K, Knott A, Mortimer K, Russell DG, Heyderman RS, Gordon SB.
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Abstract:
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Background Three billion people are exposed to household air pollution from biomass fuel use. Exposure is associated with higher incidence of pneumonia, and possibly tuberculosis. Understanding mechanisms underlying these defects would improve preventive strategies. Methods We used human alveolar macrophages obtained from healthy Malawian adults exposed naturally to household air pollution, and compared with human monocyte-derived macrophages exposed in vitro to respirable-sized particulates. Cellular inflammatory response was assessed by: IL-6 and IL-8 production in response to particulate challenge; phagocytosis of fluorescent-labelled beads and intraphagosomal oxidative burst capacity; ingestion and killing of Streptococcus pneumoniae and Mycobacterium tuberculosis measured by microscopy and quantitative culture. Particulate ingestion was quantified by digital image analysis. Results We were able to reproduce the carbon loading of naturally exposed alveolar macrophages by in vitro exposure of monocyte derived macrophages. Fine carbon black induced IL-8 release from monocyte derived and alveolar macrophages (p<0.05), with similar magnitude responses (log10 increases of 0.93 [SEM 0.2] vs 0.74 [SEM 0.19] respectively). Phagocytosis of pneumococci and mycobacteria was impaired with higher particulate loading. High particulate loading corresponded with a lower oxidative burst capacity (p=0.0015). There was no overall effect on killing of M. tuberculosis. Conclusion Alveolar macrophage function is altered by particulate loading. Our macrophage model is comparable morphologically to the in vivo uptake of particulates. Wood smoke exposed cells demonstrate reduced phagocytosis but unaffected mycobacterial killing, suggesting defects related to chronic wood smoke inhalation limited to specific innate immune functions.
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