Diesel Exhaust Particles Induce Polarization-State Dependent Functional and Transcriptional Changes in Human Monocyte-Derived Macrophages

Am J Physiol Lung Cell Mol Physiol. 2023 Dec 12. doi: 10.1152/ajplung.00085.2023. Online ahead of print.ABSTRACTMacrophage populations exist on a spectrum between the pro-inflammatory M1 and the pro-resolution M2 states and have demonstrated the ability to reprogram between them following exposure to opposing polarization stimuli. Particulate matter (PM) has been repeatedly linked to worsening morbidity and mortality following respiratory infections and has been demonstrated to modify macrophage function and polarization. The purpose of this study was to determine whether diesel exhaust particles (DEP), a key component of airborne PM, would demonstrate polarization-state dependent effects on human monocyte-derived macrophages (hMDMs) and whether DEP would modify macrophage reprogramming. CD14+CD16- monocytes were isolated from the blood of healthy human volunteers and differentiated into macrophages using macrophage colony-stimulating factor (M-CSF). Resulting macrophages were left unpolarized or polarized into the pro-resolution M2 state before being exposed to DEP, M1-polarizing conditions (IFN-γ and LPS), or both and tested for phagocytic function, secretory profile, gene expression patterns, and bioenergetic properties. Contrary to previous reports, we observed a mixed M1/M2 phenotype in reprogrammed M2 cells when considering the broader range of functional readouts. In addition, we determined that DEP exposure dampens phagocytic function in all polarization states while...
Source: Am J Physiol Lung Ce... - Category: Respiratory Medicine Authors: Source Type: research