title: 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(2)O(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 mug/ml of the dusts. AM conditioned media was analysed for lactate dehydrogenase (cytotoxicity), beta-glucuronidase (lysosomal enzyme), leukotriene B4 (LTB4), prostaglandin E(2) (PGE(2)), tumour necrosis factor alpha (TNF) and interleukin-1 (IL-1). AM LTB4 and TNF release were increased by silica and asbestos but not by Al(2)O(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 beta-glucuronidase release. The ability of silica and asbestos, but not Al(2)O(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.
authors.affiliation: The Procter & Gamble Company, Miami Valley Laboratories, Human & Environmental Safety Division, PO Box 398707, Cincinnati, OH 45239-8707, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Driscoll
authors.forename: J M
authors.initials: JM
authors.lastname: Higgins
authors.forename: M J
authors.initials: MJ
authors.lastname: Leytart
authors.forename: L L
authors.initials: LL
authors.lastname: Crosby