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Particle–Epithelial Interaction

Effect of Priming and Bystander Neutrophils on Interleukin-8 Release

Department of Environmental Health, Harvard School of Public Health, and Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts

Address correspondence to: Dr. Lester Kobzik, Physiology Program, Dept. of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115. E-mail: lkobzik{at}hsph.harvard.edu

Exposure to ambient air pollution particles causes greater health effects in individuals with preexisting inflammatory lung diseases. To model inflammatory priming in vitro, HTB54 lung epithelial cells were pretreated with tumor necrosis factor- (TNF-) and then exposed to a panel of environmental particles, including concentrated ambient particles (CAPs). TNF- priming significantly enhanced interleukin (IL)-8 secretion in response to CAPs and other urban air particles in HTB54 cells. Enhancement was seen with whole CAP suspensions as well as with its separate water-soluble and -insoluble components. Treating CAP suspensions with 20 µM deferoxamine or 2 mM dimethylthiourea attenuated the enhancement, indicating that transition metals and oxidative stress participate in the CAPs-dependent IL-8 response of primed cells. Because activated neutrophils are also present in diseased lungs and are sources of additional oxidative stress on epithelial cells, primed HTB54 cells were cocultured with activated neutrophils. Wild-type neutrophils markedly enhanced IL-8 release to CAPs in primed HTB54 cells, an effect substantially diminished when neutrophils from NADPH knockout mice were used. Cytokine priming and interactions with activated neutrophils can amplify lung epithelial inflammatory responses to ambient air particles.

Abbreviations: alveolar macrophages, AMs • bronchoalveolar lavage, BAL • concentrated ambient particles, CAPs • diethylenetriaminepenta-acetic acid, DETA • desferrioxamine, DFX • dimethylthiourea, DMTU • interleukin, IL • knockout, KO • lipopolysaccharide, LPS • macrophage inflammatory protein-2, MIP-2 • phosphate-buffered saline, PBS • polymorphonuclear neutrophils, PMNs • residual oil fly ash, ROFA • tumor necrosis factor-, TNF- • urban air particles, UAP • wild-type, WT