Iron Oxide Particles Alter Bacterial Uptake and the LPS-Induced Inflammatory Response in Macrophages

Lewis J Williams,Stephen G Tristram,Graeme R Zosky

doi:10.3390/ijerph18010146

Abstract

Exposure to geogenic (earth-derived) particulate matter (PM) is linked to severe bacterial infections in Australian Aboriginal communities. Experimental studies have shown that the concentration of iron in geogenic PM is associated with the magnitude of respiratory health effects, however, the mechanism is unclear. We investigated the effect of silica and iron oxide on the inflammatory response and bacterial phagocytosis in macrophages. THP-1 and peripheral blood mononuclear cell-derived macrophages were exposed to iron oxide (haematite or magnetite) or silica PM with or without exposure to lipopolysaccharide. Cytotoxicity and inflammation were assessed by LDH assay and ELISA respectively. The uptake of non-typeable Haemophilus influenzae by macrophages was quantified by flow cytometry. Iron oxide increased IL-8 production while silica also induced significant production of IL-1β. Both iron oxide and silica enhanced LPS-induced production of TNF-α, IL-1β, IL-6 and IL-8 in THP-1 cells with most of these responses replicated in PBMCs. While silica had no effect on NTHi phagocytosis, iron oxide significantly impaired this response. These data suggest that geogenic particles, particularly iron oxide PM, cause inflammatory cytokine production in macrophages and impair bacterial phagocytosis. These responses do not appear to be linked. This provides a possible mechanism for the link between exposure to these particles and severe bacterial infection.

Highlights

Bronchiectasis is a chronic obstructive lung disease that develops as a result of prolonged inflammation leading to structural changes in the airways and recurrent infections [1]
Quartz caused a dose-dependent increase in Lactate dehydrogenase (LDH) production, with an increase observed at the 25 μg/mL concentration (p < 0.001) and a further increase at 50 μg/mL
Exposure to LPS reduced the quartz-induced LDH production, such that an increase in LDH was only detectable in response to the 50 μg/mL dose (p < 0.001), and the LDH production at this dose was significantly lower than that of the cells exposed to the same dose of quartz without LPS (p < 0.001) (Figure 1A)

Summary

Introduction

Bronchiectasis is a chronic obstructive lung disease that develops as a result of prolonged inflammation leading to structural changes in the airways and recurrent infections [1]. The prevalence of bronchiectasis is almost three times higher in Australian. Aboriginals living in rural communities [2] and these communities have among the highest prevalence of bronchiectasis in children globally [3]. While these communities often have comparatively higher rates of smoking and restricted access to medical services [4,5,6], other environmental factors may be contributing to this disease disparity [7,8,9]. Previous studies have suggested that exposure to air pollution is associated with increased bronchiectasis exacerbations and mortality [10,11]. The potential contribution of these airborne particles to the burden of bronchiectasis is unclear

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Conclusion