Silica-induced pulmonary inflammation and fibrosis in mice is altered by acute exposure to nitrogen dioxide.
The biologic impact of consecutive exposures to two environmental pollutants was examined in mice exposed to silica crystals (SI) by intratracheal (IT) injection followed by an inhalation exposure to nitrogen dioxide (NO2). C57Bl/6 mice received an IT injection of 2 mg SI or sterile saline (SAL) followed by a 2-h inhalation exposure to NO2 at 20 ppm either within 2 h of or 24 h after SI instillation. During acute inflammation (d 3 postsilica), mice exposed to NO2 at either time showed a dramatic and significant reduction in the number of lavaged alveolar neutrophils (PMN) when compared to silica/air-exposed mice. Animals exposed to NO2 24 h after silica also evidenced significant decreases in levels of lavage albumin and lactate dehydrogenase (LDH) 3 d after silica, as well as significant decreases in hydroxyproline content of the lung 30 and 60 d postsilica injection when compared to silica/air-exposed animals. NO2 administration 24 h after silica appeared to shift the appearance of PMN in the lung from d 3 to d 14, but did not otherwise alter chronic cellular inflammation. These data suggest that the marked neutrophil response and collagen deposition induced by SI can be modulated by NO2 exposure and that the time of oxidant gas exposure after silica administration is critical to this modulation.
Vetrano
K M
KM
School of Pharmacy, University of Connecticut, Storrs 06269.
Morris
J B
JB
Hubbard
A K
AK
D000208:Acute Disease; D000393:Air Pollutants / Q000633:toxicity*; D000418:Albumins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects; D009585:Nitrogen Dioxide / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D012822:Silicon Dioxide / Q000633:toxicity*; D013997:Time Factors
D000393:Air Pollutants; D000418:Albumins; D015415:Biomarkers; D016877:Oxidants; D011506:Proteins; D012822:Silicon Dioxide; D003094:Collagen; D007770:L-Lactate Dehydrogenase; D009585:Nitrogen Dioxide