PMID- 19729031 OWN - NLM STAT- MEDLINE DCOM- 20091202 LR - 20211020 IS - 1096-0333 (Electronic) IS - 0041-008X (Print) IS - 0041-008X (Linking) VI - 241 IP - 3 DP - 2009 Dec 15 TI - Pulmonary effects of inhaled diesel exhaust in aged mice. PG - 283-93 LID - 10.1016/j.taap.2009.08.025 [doi] AB - 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 microg/m(3)) 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 (TNFalpha) 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. FAU - Sunil, Vasanthi R AU - Sunil VR AD - Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. sunilvr@eohsi.rutgers.edu FAU - Patel, Kinal J AU - Patel KJ FAU - Mainelis, Gediminas AU - Mainelis G FAU - Turpin, Barbara J AU - Turpin BJ FAU - Ridgely, Sherritta AU - Ridgely S FAU - Laumbach, Robert J AU - Laumbach RJ FAU - Kipen, Howard M AU - Kipen HM FAU - Nazarenko, Yevgen AU - Nazarenko Y FAU - Veleeparambil, Manoj AU - Veleeparambil M FAU - Gow, Andrew J AU - Gow AJ FAU - Laskin, Jeffrey D AU - Laskin JD FAU - Laskin, Debra L AU - Laskin DL LA - eng GR - U54 AR055073-03/AR/NIAMS NIH HHS/United States GR - R01 CA132624/CA/NCI NIH HHS/United States GR - R01 CA132624-02/CA/NCI NIH HHS/United States GR - U54 AR055073-02/AR/NIAMS NIH HHS/United States GR - ES013520/ES/NIEHS NIH HHS/United States GR - R01 GM034310/GM/NIGMS NIH HHS/United States GR - U54 AR055073/AR/NIAMS NIH HHS/United States GR - ES005022/ES/NIEHS NIH HHS/United States GR - K08 ES013520-04/ES/NIEHS NIH HHS/United States GR - GM034310/GM/NIGMS NIH HHS/United States GR - CA132624/CA/NCI NIH HHS/United States GR - R01 HL086621/HL/NHLBI NIH HHS/United States GR - R01 GM034310-24/GM/NIGMS NIH HHS/United States GR - AR055073/AR/NIAMS NIH HHS/United States GR - K08 ES013520-02/ES/NIEHS NIH HHS/United States GR - U54 AR055073-04/AR/NIAMS NIH HHS/United States GR - R01 ES004738-10/ES/NIEHS NIH HHS/United States GR - P30 ES005022/ES/NIEHS NIH HHS/United States GR - P30 ES005022-20/ES/NIEHS NIH HHS/United States GR - P30 ES005022-21/ES/NIEHS NIH HHS/United States GR - R01 CA132624-01/CA/NCI NIH HHS/United States GR - R01 ES004738-14/ES/NIEHS NIH HHS/United States GR - ES004738/ES/NIEHS NIH HHS/United States GR - K08 ES013520/ES/NIEHS NIH HHS/United States GR - R01 GM034310-23/GM/NIGMS NIH HHS/United States GR - R01 ES004738/ES/NIEHS NIH HHS/United States GR - K08 ES013520-03/ES/NIEHS NIH HHS/United States GR - U54 AR055073-01/AR/NIAMS NIH HHS/United States GR - R01 ES004738-15/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20090901 PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - 0 (Aerosols) RN - 0 (Antioxidants) RN - 0 (Inflammation Mediators) RN - 0 (Nitrogen Oxides) RN - 0 (Particulate Matter) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vehicle Emissions) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 1.15.1.1 (Superoxide Dismutase) SB - IM MH - Aerosols MH - Aging/*physiology MH - Animals MH - Antioxidants/metabolism MH - Bronchoalveolar Lavage Fluid/cytology MH - Immunohistochemistry MH - Inflammation Mediators/metabolism MH - L-Lactate Dehydrogenase/metabolism MH - Lung/drug effects/metabolism/pathology MH - Lung Diseases/*chemically induced/metabolism/pathology MH - Male MH - Mice MH - Nitrogen Oxides/metabolism MH - Oxidative Stress/drug effects MH - Particle Size MH - Particulate Matter/analysis/toxicity MH - Reverse Transcriptase Polymerase Chain Reaction MH - Superoxide Dismutase/metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - Vehicle Emissions/*toxicity PMC - PMC3102559 MID - NIHMS210916 EDAT- 2009/09/05 06:00 MHDA- 2009/12/16 06:00 PMCR- 2011/05/26 CRDT- 2009/09/05 06:00 PHST- 2009/05/06 00:00 [received] PHST- 2009/08/20 00:00 [revised] PHST- 2009/08/23 00:00 [accepted] PHST- 2009/09/05 06:00 [entrez] PHST- 2009/09/05 06:00 [pubmed] PHST- 2009/12/16 06:00 [medline] PHST- 2011/05/26 00:00 [pmc-release] AID - S0041-008X(09)00369-X [pii] AID - 10.1016/j.taap.2009.08.025 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 2009 Dec 15;241(3):283-93. doi: 10.1016/j.taap.2009.08.025. Epub 2009 Sep 1.