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 <i>1</i>) coal dust and humic substances (HS), a specific component of coal, complex intracellular iron from cultured cells to initiate a functional metal deficiency, <i>2</i>) the functional cell iron deficiency that results after exposure to coal dust and HS impacts an increased release of both superoxide-related products and proinflammatory mediators, and <i>3</i>) 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 nonheme concentrations. Cell exposure to coal dust and HS increased <i>1</i>) the generation of superoxide, measured using nitro blue tetrazolium reduction and an Amplex Red assay, and <i>2</i>) the 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 1 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 proinflammatory cytokines, and pneumoconiosis.<b>NEW & NOTEWORTHY</b> Following its inhalation, coal dust disrupts the homeostasis of iron in lung cells to decrease availability. This occurs through a complexation, or binding, of the cell's required iron by the coal dust. The decreased iron concentrations available to the cell initiate inflammatory and fibrotic lung injuries, with the latter recognized as coal workers' pneumoconiosis.