Effect of World Trade Center Dust Exposure and Chronic Intermittent Hypoxia on Macrophage Matrix Metalloproteinase-12 Expression in Mice

Rationale: The pathophysiologic mechanisms by which World Trade Center (WTC) dust exposure leads to pulmonary disease have not been established. Matrix metalloproteinase-12 (MMP-12) is involved in the development of pulmonary fibrosis and chronic obstructive pulmonary disease. We have previously shown that exposure of mice to WTC dust results in increased expression of matrix metalloproteinase 12 by alveolar macrophages. Matrix metalloproteinase 12 expression is regulated, in part, by oxidative stress, which is also increased after WTC dust exposure. A significant percentage of WTC dust–exposed individuals have concomitant obstructive sleep apnea, which is an added source of oxidative stress, through chronic intermittent hypoxia (CIH).Objectives: To determine if combined exposures of mice to WTC dust and CIH exacerbated matrix metalloproteinase 12 expression in alveolar macrophages.Methods: Male Balbc/J mice (12–24 wk) were treated intratracheally with phosphate-buffered saline (PBS) or WTC dust suspended...