Recovery from oxidant-mediated lung injury: Response of metallothionein, MIP-2, and MCP-1 to nitrogen dioxide, oxygen, and ozone exposures

Oxidant-induced lung injury is believed to be mediated by reactive oxygen s pecies. Recovery from oxidant exposure has been associated with pulmonary i nflammation. Inflammatory cell accumulation involves the synthesis of chemo kines, including neutrophil chemoattractants such as macrophage inflammator y protein-2 ( MIP-2) and monocyte chemoattractants such as monocyte chemoat tractant protein-1 (MCP-1). Antioxidants are the first line of defense of l ung cells against inhaled oxidants. Metallothionein (MT) can act as an anti oxidant and free-radical scavenger. To better understand the pulmonary resp onse associated with recovery from oxidant-mediated injury, we exposed mice to either 15 ppm nitrogen dioxide for 24 h, >99% oxygen for 72 h, or 1 ppm ozone for 24 h. Mice were examined at the end of exposure or after recover ing in room air for 4 or 24 h. Neutrophils were elevated at the end of expo sure and remained elevated through the postexposure period, whereas macroph age numbers were decreased at the end of exposure and remained below contro l levels at 4 and 24 h postexposure. MT, MIP-2, and MCP-1 mRNA levels were elevated at 4 h postexposure; however, after 24 h of recovery only MCP-1 re mained elevated. These results indicate that MT, MIP-2, and MCP-1 mRNA leve ls responded similarly to recovery from nitrogen dioxide, oxygen, and ozone exposure. Monocyte accumulation was delayed as compared to neutrophils and was consistent with the timing of MIP-2 and MCP-1 expression. Peak express ion of MT and MIP-2 preceded peak neutrophil accumulation. Consequently, th e timing of MT, MIP-2, and MCP-1 expression may be important biological mar kers in assessing the state of injury and recovery associated with oxidant- mediated injury.