Oxygenated metabolites of arachidonic acid (AA) are produced by the alveolar macro-phage (AM) and have been shown to mediate inflammatory reactions. We therefore assessed the production of eicosanoids by AM harvested from the lungs of rats exposed to a bituminous coal dust for 2 wk in an inhalation chamber in order to determine if AA metabolism was altered in a manner that may promote an inflammatory response in the lung. Exposure to coal dust resulted in a 66% increase in the number of AM harvested, an increase in thromboxane A2 (TxA2) and leukotriene B4 (LTBJ production to 222% and 181% of control values, respectively, and a decrease in prostaglandin E2 (PCE2) production to 62% of control values. In AM harvested from rats allowed to breath clean air for 2 wk following coal dust exposure, PCE2 production returned to control levels but TxA2 and LTB4 production remained elevated. The TxA2 synthesis inhibitor UK 38, 485 reduced TxA2 production in dust-exposed AM both immediately and 2 wk following exposure. Thus, exposure of rats to coal dust significantly alters the metabolism of AA in AM, with potentially important aspects of AA metabolism remaining altered even after a 2-wk recovery period. Based on the established role of eicosanoids in inflammatory and fibrotic processes, these results suggest that the alteration of AM eicosanoid production as a result of the inhalation of coal mine dust may be an important factor in the pathophysiology of coal workers’ pneumoconiosis.
All Science Journal Classification (ASJC) codes