Alveolar macrophage cytokine response to air pollution particles: Oxidant mechanisms

Journal Article · Thu Feb 01 04:00:00 EST 2007 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2006.11.033· OSTI ID:20976859

Imrich, Amy ^[1]; Yaoyu, Ning ^[1]; Lawrence, Joy ^[1]; Coull, Brent ^[1]; Gitin, Elena ^[1]; Knutson, Mitchell ^[2]; Kobzik, Lester ^[1]

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1. Department of Environmental Health, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115 (United States)
2. Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL (United States)

Alveolar macrophages (AMs) primed with LPS and treated with concentrated ambient air particles (CAPs) showed enhanced release of tumor necrosis factor (TNF) and provide an in vitro model for the amplified effects of air pollution particles seen in people with preexisting lung disease. To investigate the mechanism(s) by which CAPs mediate TNF release in primed rat AMs, we first tested the effect of a panel of antioxidants. N-Acetyl-L-cysteine (20 mM), dimethyl thiourea (20 mM) and catalase (5 {mu}M) significantly inhibited TNF release by primed AMs incubated with CAPs. Conversely, when LPS-primed AMs were treated with CAPs in the presence of exogenous oxidants (H{sub 2}O{sub 2} generated by glucose oxidase, 10 {mu}M/h), TNF release and cell toxicity was significantly increased. The soluble fraction of CAPs suspensions caused most of the increased bioactivity in the presence of exogenous H{sub 2}O{sub 2}. The metal chelator deferoxamine (DFO) strongly inhibited the interaction of the soluble fraction with H{sub 2}O{sub 2} but had no effect on the bioactivity of the insoluble CAPs fraction. We conclude that CAPs can mediate their effects in primed AMs by acting on oxidant-sensitive cytokine release in at least two distinct ways. In the primed cell, insoluble components of PM mediate enhanced TNF production that is H{sub 2}O{sub 2}-dependent (catalase-sensitive) yet independent of iron (DFO-insensitive). In the presence of exogenous H{sub 2}O{sub 2} released by AMs, PMNs, or other lung cells within an inflamed alveolar milieu, soluble iron released from air particles can also mediate cytokine release and cell toxicity.

• OSTI ID: 20976859
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 218; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AIR POLLUTION
ANTIOXIDANTS
CATALASE
CYSTEINE
DEFEROXAMINE
GLUCOSE
HYDROGEN PEROXIDE
IN VITRO
IRON
LUNGS
LYMPHOKINES
MACROPHAGES
OXIDASES
OXIDIZERS
RATS
RESPIRATORY TRACT CELLS
THIOUREA
TOXICITY