Effects of Diesel Exhaust Particles on Antigen-Presenting Cells and Antigen-Specific Th Immunity in Mice

Abstract

Diesel exhaust particles (DEP) exacerbate antigen-related airway inflammation and hyperresponsiveness in mice; however, the mechanisms remain undefined. The present study characterized more precisely which pathways and cellular events of the allergic response are amplified by DEP in view of the maturation/activation/function of antigen-presenting cells (APC) and the antigen-specific Th response. We evaluated the effects of DEP on the phenotype and function of bone marrow-derived dendritic cells (BMDC) in vitro and on the expression pattern of APC-related molecules in the murine lung in the presence or absence of antigen in vivo. Also, we tested the effects of in vivo DEP co-exposure with antigen on the splenic antigen-specific Th response in the context of cytokine production. DEP significantly increased both allogeneic and antigen (ovalbumin: OVA)-specific syngeneic T-cell proliferation in vitro. In addition, an in vivo experiment showed that repetitive pulmonary exposure to DEP plus antigen (OVA) increased the numbers of MHC class II+cells and those expressing CD11c, DEC205 (DC markers), CD80, CD86 (co-stimulatory molecules), F4/80 (a macrophage marker), and CD19 (a B-cell differentiation antigen) in the lung as compared to that of others (vehicle, DEP, or OVA). Furthermore, an ex vivo assay system demonstrated that splenic mononuclear cells primed by DEP plus OVA produced a greater amount of interleukin (IL)-4, IL-5, and IL-13 after in vitro antigen stimulation compared to those primed by the other treatments. In conclusion, enhancement of allergic responses by DEP can be explained via two novel mechanisms, i.e., enhancement effects on APC including DC and on antigen-specific Th response, which culminate in the promotion of local and systemic dysregulated Th immunity.

Promoting effects of nanoparticles/materials on sensitive lung inflammatory diseases

“…In addition, one intriguing aspect of the epidemiologic data is that health effects of PM 2.5 are primarily seen in subjects with predisposing factors, including pneumonia, asthma, chronic obstructive pulmonary disease, compromised immune systems, and age over 65 years old [3]. Consistent with the epidemiological studies, we have experimentally demonstrated that diesel exhaust particles (DEP), major contributors to environmental PM 2.5 in urban areas, exhibit respiratory toxicity with or without predisposing factors in vivo [4][5][6][7][8][9][10].…”

“…The concentration of particulate matter (PM) with mass median aerodynamic diameter (a density-dependent unit of measure used to describe the diameter of the particle) B2.5 lm (PM 2.5 ) is more closely associated with both acute and chronic respiratory effects and subsequent mortality than larger particles of B10 lm (PM 10 ) [2]. In addition, one intriguing aspect of the epidemiologic data is that health effects of PM 2.5 are primarily seen in subjects with predisposing factors, including pneumonia, asthma, chronic obstructive pulmonary disease, compromised immune systems, and age over 65 years old [3].…”

Diesel Exhaust Particles Stimulate Adaptive Immunity by Acting on Pulmonary Dendritic Cells

“…One could therefore speculate that DEP exposure has an impact on several aspects of the DC biology. Indeed, in vitro data demonstrated that DEP exposure induces DC maturation (10,11) via epithelial cell-derived mediators (12,13) and that DEP-exposed DCs induce a Th2 polarization (10,(13)(14)(15).…”

Biology of Diesel Exhaust Effects on Allergic Pulmonary Inflammation

“…47) In our previous study, the numbers of cells expressing MHC class II and/or co-stimulatory molecules (CD80 and CD86) in the lung were greater in the DEP＋OVA group than in the other groups. 41) Furthermore, the numbers of DC, macrophages, and B cells bearing MHC class II in the lung were also increased by the administration of DEP to antigen-sensitized mice. It can be proposed that the enhanced expression of these APC-related molecules and increased pulmonary numbers of APC in the presence of antigen induced by DEP can, at least in part, play a role in the aggravating eŠects of DEP on the allergic response in the airway as reported previously.…”

“…32,33,36,37) Several studies have identiˆed a critical role for DC in antigen-related airway in‰amma-tion. 38,39) Indeed, in vitro data demonstrated that DEP exposure induces DC maturation 40,41) via epithelial cell-derived mediators 42,43) and that DEP-exposed DC induce a Th2 polarization. 40,44,45) On the other hand, proallergic eŠects of DEP on T lymphocytes primed with in vivo antigen challenge remain obscure, although previous in vivo studies have demonstrated that DEP amplify the lung expression of Th cytokines.…”