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Quartz disrupts iron homeostasis in alveolar macrophages to impact a pro-inflammatory effect
Citation:
Ghio, Andy, J. Soukup, J. Stonehuerner, H. Tong, J. Richards, Matthew Gilmour, M. Madden, Z. Shen, AND S. Kantrow. Quartz disrupts iron homeostasis in alveolar macrophages to impact a pro-inflammatory effect. CHEMICAL RESEARCH IN TOXICOLOGY. American Chemical Society, Washington, DC, 32(9):1737-1747, (2019). https://doi.org/10.1021/acs.chemrestox.8b00301
Impact/Purpose:
Inhaled particles are phagocytized by human macrophages. This process produces a disruption to the cells iron homeostasis and results in oxidative stress and further biological effects. Using silica as a model particle, we delineated the relationship between changes in the iron homeostasis of the exposed macrophages and biological effect.
Description:
The biological response of bronchial epithelial cells to particles is associated with a sequestration of cell metal by the particle surface and a subsequent disruption in host iron homeostasis. The macrophage is that cell type resident in the respiratory tract which inhaled particles are most likely to initially contact. We tested the postulates that 1) silica, a prototypical particle, disrupts iron homeostasis in alveolar macrophages (AMs) and 2) the altered iron homeostasis results in both an oxidative stress and pro-inflammatory effects. Human AMs (1.0x106/mL) demonstrated an increased import of iron following particle exposure with non-heme iron concentrations of 0.57±0.03, 1.72±0.09, 0.88±0.09, and 3.21±0.11 ppm in cells exposed for 4 hr to media, 500 µM ferric ammonium citrate (FAC), 100 µg/mL silica, and both silica and FAC respectively. Intracellular ferritin concentrations and iron release were similarly increased after AM exposure to FAC and silica. Silica increased oxidant generation by AMs measured using both dichlorofluorescein diacetate fluorescence and reduction of nitroblue tetrazolium salt. Concentrations of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α in macrophage supernatant increased following 100 µg/mL silica exposure for 24 hr. Treatment of AMs with 500 µM FAC decreased both oxidant generation and cytokine release associated with silica exposure supporting a dependence of these effects on sequestration of cell metal by the particle surface. We conclude that 1) silica exposure disrupts iron homeostasis resulting in increased import, accumulation, and release of the metal and 2) the altered iron homeostasis following silica exposure impacts oxidant generation and pro-inflammatory effects.
URLs/Downloads:
DOI: Quartz disrupts iron homeostasis in alveolar macrophages to impact a pro-inflammatory effect