Coal fly ash- and copper smelter dust-induced modulation of ex vivo production of tumor necrosis factor-alpha by murine macrophages: Effects of metals and overload

The objective of this study was to assess the effect of two arsenic-contain ing particles, coal fly ash (FA) and copper smelter dust (CU), on lung inte grity and on the ex vivo release of tumor necrosis factor alpha (TNF-alpha) by alveolar phagocytes. Particle effects were compared in nonoverload cond ition on the basis of a low but identical volume load and arsenic content i ntratracheally instilled in the mouse lung (273 nl/mouse and 186 ng arsenic /mouse; FA(L) and CUL groups). Other mice received 600 ng arsenic/mouse in amounts of particles leading to different volume loads (FA(H) and CUH group s: 880 and 273 nl/mouse, respectively). Animals were sacrificed at 1, 6, 30 , or 120 d (FA(L) and CUL groups) or at 6 and 120 d posttreatment (FA(H) an d CUH groups). Biochemical markers and inflammatory cell number and type we re analyzed in bronchoalveolar lavage, ex vivo TNF-alpha production by alve olar phagocytes was assessed, and measurement of arsenic lung content and h istopathological examinations were performed. Our results show that coal fl y ash and copper smelter dust bear distinct inflammatory properties. At the end of the observation period (d 120), the high CU dose (CUH) produced a f ibrotic reaction whereas the high dose of FA particles (FA(H)) generated a delayed and persistent lung inflammatory reaction associated with lymphoid noduli. Marked differences in TNF-alpha production were observed within the CU and FA groups. CU particles, conceivably through their metal content, d ecreased TNF-alpha production by alveolar phagocytes. Due to their low arse nic content, considerably higher FA particle doses needed to be administere d to produce an inhibition of TNF-alpha production. Since high doses of FA (FA(H)) caused an overload condition, our results do not allow vs to decide whether FA-mediated TNF-alpha reduction is due to the load administered or to the metallic content.