title: Lipopolysaccharide priming amplifies lung macrophage tumor necrosis factor production in response to air particles.
abstract: Elevated concentrations of ambient air particles can result in increased mortality and morbidity, especially in people with preexisting pulmonary disease. We postulate that in the inflammatory milieu of diseased lungs, alveolar macrophages (AMs) may be primed for enhanced responses to stimuli such as inhaled air particles. To test this hypothesis in vitro, we first cultured normal AMs with or without lipopolysaccharide (LPS). We then incubated the cells with particle suspensions (urban air particles (UAP, Washington, D.C.), residual oil fly ash (ROFA), concentrated respirable-size (PM2.5) air particles (CAPs), and inert TiO2) and compared rat and human AM production of the critical proinflammatory mediator, tumor necrosis factor (TNF). LPS priming amplified TNF production by both rat and human AMs in response to UAP and CAPs but not inert TiO2. There were also differences observed between rat and human AM responses to particle suspensions. Striking changes seen only in rat were cytotoxic effects of ROFA and diminished particle uptake in response to LPS priming. The potency of CAPs samples (which are collected on separate days) varied when comparing one day's sample with another. When centrifuged, the majority of bioactivity seen in particle suspensions (TNF release) remained within the pelleted fraction while the supernatant showed minimal bioactivity. The data suggest that AMs activated by extant pulmonary inflammation may promote further inflammation by an enhanced cytokine response to inhaled ambient air particles.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: A
authors.initials: A
authors.lastname: Imrich
authors.forename: Y Y
authors.initials: YY
authors.lastname: Ning
authors.forename: H
authors.initials: H
authors.lastname: Koziel
authors.forename: B
authors.initials: B
authors.lastname: Coull
authors.forename: L
authors.initials: L
authors.lastname: Kobzik
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology*; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000393:Air Pollutants; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha