Wood Smoke Particle Sequesters Cell Iron to Impact a Biological Effect

Abstract

The biological effect of an inorganic particle (i.e., silica) can be associated with a disruption in cell iron homeostasis. Organic compounds included in particles originating from combustion processes can also complex sources of host cell iron to disrupt metal homeostasis. We tested the postulate that (1) wood smoke particle (WSP) sequesters host cell iron resulting in a disruption of metal homeostasis, (2) this loss of essential metal results in both an oxidative stress and biological effect in respiratory epithelial cells, and (3) humic-like substances (HULIS), a component of WSP, have a capacity to appropriate cell iron and initiate a biological effect. BEAS-2B cells exposed to WSP resulted in diminished concentrations of mitochondrial 57Fe, whereas preincubation with ferric ammonium citrate (FAC) prevented significant mitochondrial iron loss after such exposure. Cellular oxidant generation was increased after WSP exposure, but this signal was diminished by coincubation with FAC. Similarly, exposure of BEAS-2B cells to 100 μg/mL WSP activated mitogen-activated protein (MAP) kinases, elevated NF-E2-related factor 2/antioxidant responsive element (Nrf2 ARE) expression, and provoked interleukin (IL)-6 and IL-8 release, but all these changes were diminished by coincubation with FAC. The biological response to WSP was reproduced by exposure to 100 μg/mL humic acid, a polyphenol comparable to HULIS included in the WSP that complexes iron. We conclude that (1) the biological response following exposure to WSP is associated with sequestration of cell iron by the particle, (2) increasing available iron in the cell diminished the biological effects after particle exposure, and (3) HULIS included in WSP can sequester the metal initiating the cell response.

Particulate emissions from the combustion of birch, beech, and spruce logs cause different cytotoxic responses in A549 cells

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Comparison of in vitro toxicological effects of biomass smoke from different sources of animal dung

“…A majority of studies to date investigating the toxicological impact of biomass smoke have used aqueous smoke extracts or smoke particulate-containing condensates to treat submerged cell cultures, while a few have used particulates collected from homes that use dung biomass for cooking and heating (6, 7, 41–45). Here, we primarily exposed lung airway cells to whole dung biomass smoke at the air-liquid interface, and only used extracts when using non-airway reporter cell lines.…”

The “Iron”-y of Iron Overload and Iron Deficiency in Chronic Obstructive Pulmonary Disease

“…Mitochondria are the main cellular consumers of iron, and a number of vital cellular processes rely on precise mitochondrial iron regulation. Failure to correctly regulate mitochondrial iron leads to mitochondrial dysfunction, which is observed in response to wood smoke (loss of mitochondrial iron [107]) and CS (increased mitochondrial iron [33]). In mice, IRP2 deficiency protects against CS-induced COPD and CS-induced mitochondrial iron loading.…”