Abstract

Diesel exhaust particles (DEPs) are known pathogenic pollutants that constitute a significant quantity of air pollution. Given the ubiquitous presence of macrophages throughout the body, including the lungs, as well as their critical role in tissue and organismal metabolic function, we sought to determine the effect of DEP exposure on macrophage mitochondrial function. Following daily DEP exposure in mice, pulmonary macrophages were isolated for mitochondrial analyses, revealing reduced respiration rates and dramatically elevated H2O2 levels. Serum ceramides and inflammatory cytokines were increased. To determine the degree to which the changes in mitochondrial function in macrophages were not dependent on any cross-cell communication, primary pulmonary murine macrophages were used to replicate the DEP exposure in a cell culture model. We observed similar changes as seen in pulmonary macrophages, namely diminished mitochondrial respiration, but increased H2O2 production. Interestingly, when treated with myriocin to inhibit ceramide biosynthesis, these DEP-induced mitochondrial changes were mitigated. Altogether, these data suggest that DEP exposure may compromise macrophage mitochondrial and whole-body function via pathologic alterations in macrophage ceramide metabolism.

Highlights

  • Animals have two main interfaces where the body directly incorporates and transports material from the external to the internal environments

  • One of the earliest observations of this interaction was the production of inflammatory cytokines from adipose, a prototypical metabolic tissue, which resulted in defects in systemic sensitivity to insulin, a prototypical metabolic hormone [1]

  • The purpose of this study was to elucidate the effects of diesel exhaust particles, which are readily inhaled through the lungs, on the bioenergetic profile of macrophages

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Summary

Introduction

Animals have two main interfaces where the body directly incorporates and transports material from the external to the internal environments. These nexuses of interaction, the intestines and the lungs, are scrutinized in the quest to fully understand the metabolic ramifications of the immediate environment around us. Macrophages, whether adipose or otherwise, are highly relevant to this process, with a prominent line of evidence suggesting that macrophage activation provides an inflammatory “spark” that ignites systemic downstream cardiometabolic complications [2,3,4]. Insofar as the lung, being one of two sites of direct environment–host interaction, is enriched with macrophages, evidence implicating the macrophage and its inflammatory actions in metabolic disruption in response to inhaled noxious stimuli is strong [5]

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