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

Abstract

The objective of this study was to assess the effect of two arsenic-containing particles, coal fly ash (FA) and copper smelter dust (CU), on lung integrity and on the ex vivo release of tumor necrosis factor alpha (TNF-alpha) by alveolar phagocytes. Particle effects were compared in nonoverload condition on the basis of a low but identical volume load and arsenic content intratracheally instilled in the mouse lung (273 nl/mouse and 186 ng arsenic/mouse; FAL and CUL groups). Other mice received 600 ng arsenic/mouse in amounts of particles leading to different volume loads (FAH and CUH groups: 880 and 273 nl/mouse, respectively). Animals were sacrificed at 1, 6, 30, or 120 d (FAL and CUL groups) or at 6 and 120 d posttreatment (FAH and CUH groups). Biochemical markers and inflammatory cell number and type were analyzed in bronchoalveolar lavage, ex vivo TNF-alpha production by alveolar phagocytes was assessed, and measurement of arsenic lung content and histopathological examinations were performed. Our results show that coal fly 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 fibrotic reaction whereas the high dose of FA particles (FAH) 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, decreased TNF-alpha production by alveolar phagocytes. Due to their low arsenic content, considerably higher FA particle doses needed to be administered to produce an inhibition of TNF-alpha production. Since high doses of FA (FAH) caused an overload condition, our results do not allow us to decide whether FA-mediated TNF-alpha reduction is due to the load administered or to the metallic content.

Understanding the Chemical Properties of Macerals and Minerals in Coal and its Potential Application for Occupational Lung Disease Prevention

“…The oxidative property of coal dusts is primarily attributed to its transition metal constituents, which typically include Fe, Cr, Co, Ni, Mn, As, Zn, and V (Broeckaert et al, 1999;Finkelman, 1999;Zhang et al, 2002). Using electron spin resonance (ESR), it was found that aqueous coal filtrates containing Fe, Zn, Cu, Ni, and Co were able to produce ROS such as • OH or ferryl (Fe IV =O) (Huang et al, 1993).…”

“…Due to the mixed nature of various chemical compositions in these dusts, it is extremely difficult to identify the active compound(s) in the dusts that is responsible for the disease (Broeckaert et al, 1999;Costa & Dreher, 1997). Recently, progress has been made in metal-induced parenchymal lung disorders.…”

Effects of submicrometer particle compositions on cytokine production and lipid peroxidation of human bronchial epithelial cells.

“…Transition metals may enhance intracellular production of oxidants, with ensuing cell activation or injury. Metal-containing residual oil fly ash, coal fly ash, and some transition metals were found to result in enhanced expression of proinflammatory cytokines in cell culture systems (Broeckaert et al 1999;Dye et al 1999;Samet et al 1998;Smith et al 2000). However, there has been little direct evidence correlating cellular responses with ambient particle components.…”

An evaluation of the toxicological aspects and potential doses from the inhalation of coal combustion products

“…However, work by Broeckaet and colleagues has shown that coal fly ash can inhibit TNF-a release in alveolar macorophages (Broeckaert et al, 1999;Broeckaert et al, 1997). Work by Smith et al (2006) showed that rats exposed to high concentrations of PM 2.5 (1.4 mg/m 3 ) and PM 1 (600 µg/m 3 ) of coal fly ash for 4 hr/day for 3 days had a mild neutrophilic inflammatory response in the lungs and blood (Smith et al, 2006).…”

“…While recent, as well as earlier, reports have shown little to no adverse effects after inhalation exposure, others have shown that fly ash particles can activate alveolar macrophage and epithelial cells can cause the release of inflammatory mediators; can alter lung permeability; and can generate reactive oxygen species (ROS), enzymes such as elastase, proteases, and collagenases, cytokines such as TNF-a and MIP-1, and growth factors such as TGF-b (Borm, 1997;Fernandez et al, 2002;Fernandez et al, 2003;Broeckaert et al, 1999). However, work by Broeckaet and colleagues has shown that coal fly ash can inhibit TNF-a release in alveolar macorophages (Broeckaert et al, 1999;Broeckaert et al, 1997).…”