Acute No2exposure alters inflammatory cell activation and particle clearance in silica‐injected mice

Abstract

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 inter‐stitial 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.