Silica‐induced pulmonary inflammation and fibrosis in mice is altered by acute exposure to nitrogen dioxide

Abstract

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 silical 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 silicalair‐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.