title: Household air pollution causes dose-dependent inflammation and altered phagocytosis in human macrophages.
abstract: 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. We used human alveolar macrophages obtained from healthy Malawian adults exposed naturally to household air pollution and compared them 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; phagosomal function was tested by uptake and oxidation of fluorescence-labeled beads; ingestion and killing of Streptococcus pneumoniae and Mycobacterium tuberculosis were measured by microscopy and quantitative culture. Particulate ingestion was quantified by digital image analysis. 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] versus 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. 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.
authors.affiliation: 1 Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rylance
authors.forename: Duncan G
authors.initials: DG
authors.lastname: Fullerton
authors.forename: James
authors.initials: J
authors.lastname: Scriven
authors.forename: Abdullah N
authors.initials: AN
authors.lastname: Aljurayyan
authors.forename: David
authors.initials: D
authors.lastname: Mzinza
authors.forename: Steve
authors.initials: S
authors.lastname: Barrett
authors.forename: Adam K A
authors.initials: AK
authors.lastname: Wright
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Wootton
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Glennie
authors.forename: Katy
authors.initials: K
authors.lastname: Baple
authors.forename: Amy
authors.initials: A
authors.lastname: Knott
authors.forename: Kevin
authors.initials: K
authors.lastname: Mortimer
authors.forename: David G
authors.initials: DG
authors.lastname: Russell
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gordon
mesh_terms: D000328:Adult; D000368:Aged; D000393:Air Pollutants / Q000009:adverse effects*; D016902:Air Pollution, Indoor / Q000009:adverse effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004739:England; D006798:Housing; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D019570:Inhalation Exposure / Q000009:adverse effects; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008295:Malawi; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects*; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D053260:Soot / Q000009:adverse effects*; D013296:Streptococcus pneumoniae / Q000276:immunology; D014934:Wood / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000393:Air Pollutants; C508606:CXCL8 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D053260:Soot
keywords: Mycobacterium tuberculosis; Streptococcus pneumoniae; alveolar macrophages; indoor air pollution; innate immunity