Acute NO2 exposure alters inflammatory cell activation and particle clearance in silica-injected mice.
Previous work indicates that exposure to nitrogen dioxide (NO2) at different stages of silica-induced acute inflammation alters the outcome of lung injury. C57BI/6 mice were injected intratracheally (IT) with 2.0 mg silica particles (SI) and subsequently exposed to 20 ppm NO2 (or filtered air) within 2 or 24 h after SI. The present study demonstrates that exposure of mice to NO2 within 2 h after silica injection during acellular lung injury (increased alveolar protein, albumin, lactate dehydrogenase) resulted in increases in intraalveolar and interstitial polymorphonuclear leukocytes (PMNs) as well as more advanced granulomas on d 14, 30, and 60. In contrast, exposure of mice to NO2 24 h after silica during marked lung injury and inflammatory cell influx resulted in a less severe inflammatory reaction with fewer interstitial and alveolar PMNs and decreased size and number of pulmonary granulomas. NO2 exposure 2 or 24 h after SI appeared to increase in the lavage fluid levels of lysosomal enzymes and at the same time decrease levels of PMN chemotactins. Moreover, exposure to NO2 24 h after SI significantly decreased SI accumulation in the mediastinal lymph nodes. These data suggest that NO2 modulation of SI lung injury may be due, in part, to changes in inflammatory cell activation/influx and/or altered particle disposition within the lung. These effects are dependent upon the inflammatory status of SI exposed lungs at the time NO2 is administered.
Hubbard
A K
AK
Section of Pharmacology/Toxicology, School of Pharmacy, University of Connecticut, Storrs 06269.
Vetrano
K M
KM
Morris
J B
JB
Thrall
R S
RS
D000818:Animals; D001273:Atmosphere Exposure Chambers; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003094:Collagen / Q000737:chemistry; D004347:Drug Interactions; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009585:Nitrogen Dioxide / Q000494:pharmacology*; D012822:Silicon Dioxide / Q000633:toxicity*
D012822:Silicon Dioxide; D003094:Collagen; D009585:Nitrogen Dioxide