title: Exposure of brown Norway rats to diesel exhaust particles prior to ovalbumin (OVA) sensitization elicits IgE adjuvant activity but attenuates OVA-induced airway inflammation.
abstract: Exposure to diesel exhaust particles (DEP) during the sensitization process has been shown to increase antigen-specific IgE production and aggravate allergic airway inflammation in human and animal models. In this study, we evaluated the effect of short-term DEP exposure on ovalbumin (OVA)-mediated responses using a post-sensitization model. Brown Norway rats were first exposed to filtered air or DEP (20.6 +/- 2.7 mg/m3) for 4 h/day for five consecutive days. One day after the final air or DEP exposure (day 1), rats were sensitized with aerosolized OVA (40.5 +/- 6.3 mg/m3), and then again on days 8 and 15, challenged with OVA on day 29, and sacrificed on days 9 or 30, 24 h after the second OVA exposure or the final OVA challenge, respectively. Control animals received aerosolized saline instead of OVA. DEP were shown to elicit an adjuvant effect on the production of antigen-specific IgE and IgG on day 30. At both time points, no significant airway inflammatory responses and lung injury were found for DEP exposure alone. However, the OVA-induced inflammatory cell infiltration, acellular lactate dehydrogenase activity and albumin content in bronchoalveolar lavage (BAL) fluid, and numbers of T cells and their CD4+ and CD8+ subsets in lung-draining lymph nodes were markedly reduced by DEP on day 30 compared with the air-plus-OVA exposure group. The OVA-induced nitric oxide (NO) in the BAL fluid and production of NO, interleukin (IL)-10, and IL-12 by alveolar macrophages (AM) were also significantly lowered by DEP on day 30 as well as day 9. DEP or OVA alone decreased intracellular glutathione (GSH) in AM and lymphocytes on days 9 and 30. The combined DEP and OVA exposure resulted in further depletion of GSH in both cell types. These results show that short-term DEP exposure prior to sensitization had a delayed effect on enhancement of the sensitization in terms of allergen-specific IgE and IgG production, but caused an attenuation of the allergen-induced airway inflammatory responses.
authors.affiliation: School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506-9530, USA.
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Dong
authors.forename: Xuejun J
authors.initials: XJ
authors.lastname: Yin
authors.forename: Jane Y C
authors.initials: JY
authors.lastname: Ma
authors.forename: Lyndell
authors.initials: L
authors.lastname: Millecchia
authors.forename: Mark W
authors.initials: MW
authors.lastname: Barger
authors.forename: Jenny R
authors.initials: JR
authors.lastname: Roberts
authors.forename: Xing-Dong
authors.initials: XD
authors.lastname: Zhang
authors.forename: James M
authors.initials: JM
authors.lastname: Antonini
authors.forename: Joseph K H
authors.initials: JK
authors.lastname: Ma
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000393:Air Pollutants / Q000276:immunology / Q000633:toxicity*; D000485:Allergens / Q000009:adverse effects / Q000276:immunology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000276:immunology; D001991:Bronchitis / Q000139:chemically induced* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D019570:Inhalation Exposure; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000276:Adjuvants, Immunologic; D000393:Air Pollutants; D000485:Allergens; D016207:Cytokines; D001335:Vehicle Emissions; D009569:Nitric Oxide; D007073:Immunoglobulin E; D010047:Ovalbumin; D007770:L-Lactate Dehydrogenase; D005978:Glutathione