Surface complexation of cell iron following particle exposure can be relevant to coal mine dust lung disease. We tested the postulate that 1) coal dust and humic substances (HS), a specific component of coal, complex intracellular iron from cultured cells to initiate a functional metal deficiency, 2) the functional cell iron deficiency which results after exposure to coal dust and HS impacts an increased release of both superoxide-related products and pro-inflammatory mediators, and 3) the disruption in iron homeostasis after coal dust exposure is associated with pneumoconiosis in miners. Cell exposures to coal dust and HS initiated a functional iron deficiency, reflected by elevated expression of an importer (divalent metal transporter-1), which increased metal uptake measured as cell non-heme concentrations. Cell exposure to coal dust and HS increased 1) generation of superoxide, measured using Nitroblue Tetrazolium reduction and an Amplex Red assay, and 2) release of interleukin (IL)-6 and IL-8. These measures of oxidative stress and inflammatory mediator release were diminished with co-exposure to iron supporting a relationship of both with a functional cell deficiency of the metal. Using a cohort of retired miners, blood ferritin levels were elevated in those diagnosed with a positive B read for coal workers' pneumoconiosis. Elevated blood ferritin concentrations correlated with progression of disease on B reads obtained one year later in the miners. It is concluded that coal dust and HS can initiate a disruption of iron homeostasis associated with superoxide generation, release of pro-inflammatory cytokines, and pneumoconiosis.
Ghio et al. (Sat,) studied this question.