| Condensed vapors of metals are associated by epidemiological studies with an increased risk for developing occupational lung disease due to welding activities. Chromium, nickel and manganese are predominant metals in welding fumes. In this study, chromium(VI) and manganese, but not nickel, are cytotoxic to normal human lung epithelial cells in vitro (SAEC and BEAS-2B), at concentration ranges correlated to concentrations of these metals found in welding fumes. Chromium(VI) and manganese (0.2–200 μM) caused 64% and 60% loss of cell viability, respectively, following 24 hrs exposure. The toxic effect was associated with increased levels of intracellular phosphoprotein and subsequent release of inflammatory cytokines IL-6 and IL-8, while no release of TNF-α, GM-CSF or IL-1β was observed. Changes in phosphoprotein levels and cytokine release were apparent within I hour following metal treatment. IL-6 and IL-8 are released from lung epithelium to recruit cells of the immune system to sites of tissue damage, manifesting in an inflammatory response and the initiation of repair mechanisms. Therefore, the observed effects of chromium(VI) and manganese in lung epithelial cells demonstrate a mechanism through which the toxicity of these metals can result in signaling to the immune system. This illustrates a potential connection between epithelial intoxication and manifestations of respiratory disease. |
