Coal dust complexes host cell iron to impact metal homeostasis and pneumoconiosis

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.