Diesel exhaust particles induce a Th2 phenotype in mouse naïve mononuclear cells in vitro

Abstract

It has been shown that pulmonary exposure to diesel exhaust particles (DEP) exacerbates allergic manifestations (i.e., allergic asthma) in vivo. However, the underlying mechanisms remain enigmatic. Furthermore, DEP components responsible for the exacerbation remain unidentified. Hypothesizing that DEP induce a helper T (Th)2-biased condition in immune mononuclear cells even in the absence of an allergen, the present study elucidated the effects of DEP and their components on the characterization of primary splenocytes and T cells in vitro. ICR mouse-derived splenic mononuclear and T cells isolated from the splenocytes were co-cultured with organic chemicals in DEP extracted with dichloromethane (DEP-OC 0.5-50 µg/ml), residual carbonaceous nuclei of DEP (washed DEP 0.5-50 µg/ml) or ‘whole’ DEP (1-100 µg/ml); thereafter, interleukin (IL)-4 and IgE production by these cells and the surface expression of CD19, IL-4R, CD69 and the CD40 Ligand (L) were evaluated by means of ELISA and flow cytometry. DEP and their components increased IL-4 and total IgE levels in a concentration-dependent manner 24 h after culture, and the effects were greater with washed DEP than with DEP-OC. On the other hand, each DEP component increased the surface expression of CD19 on splenocytes and that of IL-4R, CD69 or CD40L on both splenocytes and isolated T cells; however, the impact was greater with DEP-OC. These results suggest that DEP cause naïve mononuclear cells, including T cells to enter a Th2-biased state and that each DEP component plays a differential role in the efficacy.