The Effects of Coal Mine Dust Particles on the Metabolism of Arachidonic Acid by Pulmonary Alveolar Macrophages

The pulmonary alveolar macrophage is a major defensive cell which counteracts the invasive properties of bacteria and particles when these substances invade the pulmonary environment. Pulmonary exposure to coal dust particles is believed to activate these macrophages to release a host of d1emical mediators which can neutralize or contribute to the harmful effects of these dust particles. Our efforts have been concerned with assessing a specific family of mediator substances produced by the alveolar macrophage from arachidonic acid when these cells are in contact with activating substances such as coal dust. Metabolites of arachidonic acid produce a vast array of effects which can impact significantly on pulmonary function both with normal pulmonary events and with pathologic processes of the lung. Our studies demonstrate that isolated alveolar macrophages obtained from rats or guinea pigs cultured in vitro release appreciable amounts of the cyclooxygenase products prostaglandin E2 and thromboxane A2 and release significant amounts of the lipoxygenase products .5-HETE and LTB4. In the presence of l x 104 -1x10·7 g/ml of a coal dust suspension, alveolar macrophages from the rats and guinea pigs alters their pattern of arachidonic acid metabolite release. In the rat, exposure of alveolar macrophages in vitro to the higher concentrations of coal dust causes a significant reduction in PGE2, TXB2 and LTB4 in a 4 hour time course study. In contrast, macrophages from the guinea pig in response to coal dust had little change in TXB2 release, only a slight inhibition in PGE2 production and an initial stimulation in LTB.t release over the 4 hour time course. Cells from guinea pigs released considerably more TXB2 than the rat under these conditions while rat cells formed considerably more LTB4 than guinea pig alveolar macrophages. These findings support the following conclusions.