Pulmonary effects of inhaled diesel exhaust in aged mice.
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.
Sunil
Vasanthi R
VR
Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. sunilvr@eohsi.rutgers.edu
Patel
Kinal J
KJ
Mainelis
Gediminas
G
Turpin
Barbara J
BJ
Ridgely
Sherritta
S
Laumbach
Robert J
RJ
Kipen
Howard M
HM
Nazarenko
Yevgen
Y
Veleeparambil
Manoj
M
Gow
Andrew J
AJ
Laskin
Jeffrey D
JD
Laskin
Debra L
DL
D000336:Aerosols; D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009589:Nitrogen Oxides / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D052638:Particulate Matter / Q000032:analysis / Q000633:toxicity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
D000336:Aerosols; D000975:Antioxidants; D018836:Inflammation Mediators; D009589:Nitrogen Oxides; D052638:Particulate Matter; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase