Aqueous PM2.5 promotes lipid accumulation, classical macrophage polarisation and heat shock response

Fine particulate matter (PM2.5) is an air pollutant that enhances susceptibility to cardiovascular diseases. Macrophages are the first immune cells to encounter the inhaled particles and orchestrate an inflammatory response. Given their role in atherosclerosis development, we investigated whether aqueous PM2.5 could elicit atherogenic effects by polarising macrophages to a pro-oxidative and pro-inflammatory phenotype and enhancing foam cell formation. The RAW264.7 macrophage cell line was exposed to PM2.5 for 48 h, with PBS as the control. Aqueous PM2.5 induced apoptosis and reduced cell proliferation. In surviving cells, we observed morphological, phagocytic, oxidative, and inflammatory features (i.e. enhanced iNOS, Integrin-1β, IL-6 expression), indicative of classical macrophage activation. We also detected an increase in total and surface HSP70 levels, suggesting macrophage activation. Further, exposure of high-cholesterol diet-fed mice to PM2.5 resulted in aortic wall enlargement, indicating vascular lesions. Macrophages exposed to PM2.5 and non-modified low-density lipoprotein (LDL) showed exacerbated lipid accumulation. Given the non-oxidised LDL used and the evidence linking inflammation to disrupted cholesterol negative feedback, we hypothesise that PM2.5-induced inflammation in macrophages enhances their susceptibility to transforming into foam cells. Finally, our results indicate that exposure to aqueous PM2.5 promotes classical macrophage activation, marked by increased HSP70 expression and that it potentially contributes to atherosclerosis. [Display omitted] •Aqueous PM2.5 is cytotoxic to macrophage.•Aqueous PM2.5 stimulates macrophage phagocytic activity.•Aqueous PM2.5 polarises macrophages to an oxidative and inflammatory phenotype.•HSP70 may mark macrophage reactivation in polluted conditions.•PM2.5 enhances lipid accumulation by macrophage.