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The effects of ambient particulate matter on human alveolar machrophage oxidative and inflammatory responses
Citation:
Sawyer, K., S. Mundanhara, A. J. GHIO, AND M. C. MADDEN. The effects of ambient particulate matter on human alveolar machrophage oxidative and inflammatory responses. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART A: CURRENT ISSUES. Taylor & Francis, Inc., Philadelphia, PA, 73(1):41-57, (2010).
Impact/Purpose:
research results
Description:
Epidemiologic and occupational studies demonstrate that ambient PM and DEP have deleterious effects on human cardiopulmonary health including exacerbation of pre-existing lung disease and development of respiratory infections. The effects of ambient PM on lung cell responsiveness are poorly defined. Human alveolar macrophages (AM) were exposed to SRM 1649 (Washington, DC urban dust; UD), SRM 2975 (forklift diesel exhaust particles; DEP), and fine and coarse ambient PM collected in Chapel Hill, NC during the late fall (November) and early summer (June). AM were subsequently incubated with lipopolysaccharide (LPS), phorbol-myristate acetate (PMA), or calcium ionophore A23817 for 6 or 24hours after PM exposure. UD and DEP suppressed O2- release 24hours post PM exposure (p<0.01). UD exposure suppressed TNF-α (p<0.05), IL-6 (p<0.01), and IL-8 (p<0.05) release after exposure to 1-ηg/mL LPS. DEP suppressed only TNF-α (p<0.01) and IL-6 release (p<0.01). Suppressed cytokine release appears to be the result of an inhibited cytokine release from the AM, but may also be caused by reduced total cytokine production. The data suggest that the decreased cytokine release is not caused by the presence of benzo(a)pyrene, a polycyclic aromatic hydrocarbon. Comparison of TNF-α release after LPS, PMA, or A23817, reveals that suppressive effects of UD is LPS-dependent, whereas, suppressive effect of DEP may work across multiple mechanistic pathways. November and June Chapel Hill PM exposure stimulated TNF-α and IL-8 release before LPS exposure. Fine (p<0.01) and coarse (p<0.05) November PM exposure suppressed TNF-α release 6h after LPS stimulation, but appeared to cause stimulatory effect on IL-8 24h after LPS exposure. June fine and coarse PM suppressed IL-8 release after LPS exposure. These data suggest that seasonal influences on PM composition can affect AM inflammatory response before and after bacterial exposure. Overall, delayed or inhibited AM immune responses to LPS after PM exposure suggests human exposure to ambient PM may enhance pulmonary susceptibility to respiratory infections. Keywords: particulate matter, diesel exhaust particle, macrophage, superoxide, cytokine
