ACUTE NO2 EXPOSURE ALTERS INFLAMMATORY CELL ACTIVATION AND PARTICLE CLEARANCE IN SILICA-INJECTED MICE

Previous work indicates that exposure to nitrogen dioxide (NO2) at dif ferent stages of silica-induced acute inflammation alters the outcome of lung injury. C57Bl/6 mice were injected intratracheally (IT) with 2 .0 mg silica particles (Sl) and subsequently exposed to 20 ppm NO2 (or filtered air) within 2 or 24 h after Sl. The present study demonstrat es that exposure of mice to NO, within 2 h after silica injection duri ng acellular lung injury (increased alveolar protein, albumin, lactate dehydrogenase) resulted in increases in intraalveolar and interstitia l polymorphonuclear leukocytes (PMNs) as well as more advanced granulo mas on d 14, 30, and 60. In contrast, exposure of mice to NO2 24 h aft er silica during marked lung injury and inflammatory cell influx resul ted 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 Sl appeared to increase in the lavage flu id levels of lysosomal enzymes and at the same time decrease levels of PMN chemotactins. Moreover, exposure to NO2 24 h after 51 significant ly decreased Sl accumulation in the mediastinal lymph nodes. These dat a suggest that NO2 modulation of 51 lung injury may be due, in part, t o changes in inflammatory cell activation/influx and/or altered partic le disposition within the lung. These effects are dependent upon the i nflammatory status of Sl exposed lungs at the time NO2 is administered .