Differential effects of mineral dusts on the in vitro activation of alveolar macrophage eicosanoid and cytokine release

Abstract

We investigated the in vitro effects of the pneumotoxic agents, silica and asbestos, and the relatively innocuous materials, aluminium oxide (Al 2O 3) and titanium dioxide (TiO 2), on alveolar macrophages (AM) using endpoints reflecting the cytotoxic and AM activating properties of the dusts. Rat AM were exposed in vitro (24 hr) to 10–1000 μg/ml of the dusts. AM conditioned media was analysed for lactate dehydrogenase (cytotoxicity), β-glucuronidase (lysosomal enzyme), leukotriene B4 (LTB4), prostaglandin E 2 (PGE 2), tumour necrosis factor α (TNF) and interleukin-1 (IL-1). AM LTB4 and TNF release were increased by silica and asbestos but not by Al 2O 3 or TiO 2. IL-1 release was not affected, and changes in PGE 2 release were minimal, after dust exposure. Cytotoxic activity was not consistently associated with LTB4, TNF or β-glucuronidase release. The ability of silica and asbestos, but not Al 2O 3 and TiO 2, to activate AM to release the pro-inflammatory mediators, LTB4 and TNF, may be responsible, at least in part, for the greater inflammation and pneumotoxicity associated with silica and asbestos exposure. These findings suggest that assessment of AM mediator secretion in vitro can provide information to understand better the potential of a material to cause respiratory toxicity.