The role of inflammation, oxidative stress, and proliferation in silica-induced lung disease: a species comparison.

Abstract

To gain a better understanding of the complex mechanisms at work in silica-induced lung disease, we conducted studies comparing the rat and hamster response to silica (alpha-quartz). It has been hypothesized that the rat lung response to low-solubility particles, such as silica, may be due to the recruitment, activation, and subsequent release of damaging mediators by the inflammatory cells. Studies have suggested that hamsters and mice may be less sensitive to the inflammatory and tumorigenic effects of these low-solubility particles than rats. Differences in defense mechanisms, such as antioxidant levels or repair mechanisms, may play a key role in how different species respond to these particles. To investigate species differences in silica-induced lung response, this study compared the effects of alpha-quartz on rats and hamsters. Briefly, rats and hamsters were intratracheally instilled with saline or 0.2, 2, or 20 mg of alpha-quartz. Seven days after exposure, bronchoalveolar lavage (BAL) was performed, and the BAL fluid was evaluated for cell number, type, and LDH. In addition, lung tissue was evaluated for the expression of various pro- and anti-inflammatory mediators. Both species showed dose-related increases in neutrophils and LDH after alpha-quartz exposure; however, the changes were significantly greater in the rat, and rats showed greater expression of several pro-inflammatory mediators and lower levels of the anti-inflammatory mediators. These differences in pro- and anti-inflammatory mediators may contribute to the apparent species differences in tumor response. A basic understanding of the different responses of various species to these inhaled toxins will contribute to our understanding of the mechanisms involved in human disease.