Cytotoxicity of chromium and manganese to lung epithelial cells in vitro

Chromium, nickel and manganese are the predominant metals in welding fumes and are associated through epidemiological studies with an increased risk for developing occupational asthma due to welding activities. Here, we show that chromium(VI) and manganese, but not nickel, are cytotoxic to normal human lung epithelial cells in vitro (SAEC and BEAS-2B), at concentration ranges of 0.2-200 microM. 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-alpha was observed. Changes in intracellular phosphoprotein levels occurred at concentrations below the cytotoxic effect. IL-6 and IL-8 production increased up to 4.4-fold relative to controls. IL-6 and IL-8 are released from lung epithelium to recruit cells of the immune system to sites of tissue damage. Therefore, the observed effects of chromium(VI) and manganese in lung epithelial cells demonstrate a mechanism through which the toxicity of these metals to epithelial cells can result in recruitment of cells of the immune system.