Pulmonary effects of inhaled diesel exhaust in aged mice

Vasanthi R. Sunil, Kinal J. Patel, Gediminas Mainelis, Barbara J. Turpin, Sherritta Ridgely, Robert J. Laumbach, Howard M. Kipen, Yevgen Nazarenko, Manoj Veleeparambil, Andrew J. Gow, Jeffrey D. Laskin, Debra L. Laskin

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    27 Citations (Scopus)

    Abstract

    Pulmonary morbidity and mortality resulting from exposure to fine particulate matter (PM) increases with age. The present studies analyzed potential mechanisms underlying increased susceptibility of the elderly to PM using diesel exhaust (DE) as a model. Mice (2 m and 18 m) were exposed to DE (0, 300, and 1000 μg/m3) for 3 h once (single) or 3 h/day for 3 days (repeated). Bronchoalveolar lavage fluid (BAL), serum and lung tissue were collected 0 and 24 h later. Exposure to DE resulted in structural alterations in the lungs of older but not younger mice, including patchy thickening of the alveolar septa and inflammatory cell localization in alveolar spaces. These effects were most pronounced 24 h after a single exposure to the higher dose of DE. Significant increases in BAL nitrogen oxides were also noted in older mice, as well as expression of lipocalin 24p3, an oxidative stress marker in the lung with no effects in younger mice. Following DE inhalation, expression of Tumor Necrosis Factor alpha (TNFα) was upregulated in lungs of both younger and older mice; however, this was attenuated in older animals. Whereas exposure to DE resulted in increases in lung Interleukin-6 (IL-6) expression in both older and younger mice, IL-8 increased only in older animals. In younger mice, constitutive expression of manganese superoxide dismutase (MnSOD) decreased after DE exposure, while in older mice, constitutive MnSOD was not detectable and DE had no effect on expression of this antioxidant. Taken together, these results suggest that altered generation of inflammatory mediators and MnSOD may contribute to increased susceptibility of older mice to inhaled DE.

    Original languageEnglish
    Pages (from-to)283-293
    Number of pages11
    JournalToxicology and Applied Pharmacology
    Volume241
    Issue number3
    DOIs
    Publication statusPublished - 15 Dec 2009

    Keywords

    • Aging
    • Antioxidants
    • Diesel exhaust
    • Lipocalin
    • Nitrogen oxides

    ASJC Scopus subject areas

    • Pharmacology
    • Toxicology

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  • Cite this

    Sunil, V. R., Patel, K. J., Mainelis, G., Turpin, B. J., Ridgely, S., Laumbach, R. J., Kipen, H. M., Nazarenko, Y., Veleeparambil, M., Gow, A. J., Laskin, J. D., & Laskin, D. L. (2009). Pulmonary effects of inhaled diesel exhaust in aged mice. Toxicology and Applied Pharmacology, 241(3), 283-293. https://doi.org/10.1016/j.taap.2009.08.025