Effects of diesel exhaust particles on macrophage polarization

Abstract

<jats:sec><jats:title>Background:</jats:title><jats:p> Exposure to diesel exhaust particles (DEP) has long been associated with increased cardiovascular morbidity and mortality. The development of DEP toxicity seems to be linked to inflammation in which macrophages play a critical role. Macrophages can be polarized into proinflammatory M1 or anti-inflammatory M2 macrophages. The aim of this study was to identify the role of inflammation in DEP-induced toxicity by assessing the effects of DEP on macrophage polarization. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> Monocyte-derived macrophages (Mϕ) were stimulated with interferon γ and lipopolysaccharide or interleukin (IL)-4 to obtain M1 and M2 subtypes, respectively. To test the polarization capacity of DEP, Mϕ cells were exposed to DEP and compared to Mϕ, M1, and M2. We also studied the effects of DEP on already-polarized M1 or M2. The M1 markers assessed were tumor necrosis factor α (TNF-α) and IL-1β, while the M2 markers were the mannose receptor C type 1 (MRC-1) and transglutaminase 2 (TGM2). </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Western blots revealed a 31 kDa band corresponding to pro-IL-1β, but only in M1-polarized macrophages. In M1, we also observed an upregulation of TNF-α messenger RNA (mRNA) expression. MRC-1 and TGM2 mRNA expression were only significantly enhanced in M2. DEP had no effect on any of the M1/M2 markers assessed. Moreover, DEP were not able to modify the phenotype of already-polarized M1 or M2. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> Mϕ incubation with DEP did not have any effect on macrophage polarization, at least on the markers assessed in this study, namely, TNF-α/IL-1β for M1, and MRC-1/TGM2 for M2. Hence, these data argue against an important role of inflammation in DEP-induced vascular toxicity. </jats:p></jats:sec>

Multi-cellular human bronchial models exposed to diesel exhaust particles: assessment of inflammation, oxidative stress and macrophage polarization

“…Large differences in sensitivity between species and within different strains of the same species have also been observed. The response to DEP exposure has been examined in in vitro studies employing airway epithelial cells, nasal epithelial cells, alveolar macrophages, mast cells, and cell lines [ 11 – 13 ]. These studies have shown that DEP can generate reactive oxygen species (ROS), which in turn trigger a variety of cellular consequences, such as DNA damage, apoptosis and inflammatory responses [ 14 , 15 ].…”

“…The lung microenvironment has been shown to influence MQ phenotype- and function [ 33 ]. However, most in vitro studies [ 11 , 34 ] investigating the cellular inflammatory response to air pollutants have used mono-culture systems, which do not address the interaction between different cell types present in the airways, and have limited applicability to in vivo situations. The cross talk between MQ and epithelial cells are essential as they both function within the first line of defense against inhaled toxic agents in both upper- and lower airways.…”