Induction of immune tolerance and reduction of aggravated lung eosinophilia by co-exposure to Asian sand dust and ovalbumin for 14 weeks in mice

Miao He; Takamichi Ichinose; Seiichi Yoshida; Hirohisa Takano; Masataka Nishikawa; Guifan Sun; Takayuki Shibamoto

doi:10.1186/1710-1492-9-19

Induction of immune tolerance and reduction of aggravated lung eosinophilia by co-exposure to Asian sand dust and ovalbumin for 14 weeks in mice

Allergy Asthma Clin Immunol. 2013 Jun 3;9(1):19. doi: 10.1186/1710-1492-9-19. eCollection 2013.

Authors

Miao He¹, Takamichi Ichinose², Seiichi Yoshida², Hirohisa Takano³, Masataka Nishikawa⁴, Guifan Sun⁵, Takayuki Shibamoto⁶

Affiliations

¹ Department of Health Sciences, Oita University of Nursing and Health Sciences, 870-1201 Oita, Japan ; Department of Environmental and Occupational Health, College of Public Health, China Medical University, 11001 Shenyang, China.
² Department of Health Sciences, Oita University of Nursing and Health Sciences, 870-1201 Oita, Japan.
³ Department of Environmental Engineering, Environmental Health Division, Graduate School of Engineering, Kyoto University, Kyoto daigaku-Katsura, Nishikyo-ku, Kyoto 615-8530, Japan.
⁴ Environmental Chemistry Division, National Institute for Environmental Studies, 305-8506 Tsukuba, Ibaraki, Japan.
⁵ Department of Environmental and Occupational Health, College of Public Health, China Medical University, 11001 Shenyang, China.
⁶ Department of Environmental Toxicology, Takayuki Shibamoto, University of California, Davis, CA 95616,, USA.

Abstract

Background: Atmospheric contamination caused by Asian sand-dust (ASD) storms aggravates asthma in both human adults and children. This study aims to investigate a series of manifestations in allergic airway disease caused by co-exposure to allergens and ASD for 6 weeks and 14 weeks.

Methods: CD-1 Mice were instilled intratracheally with 0.1 mg of ASD/mouse four times (6 weeks) or eight times (14 weeks) at 2-week intervals (total dose of 0.4 mg or 0.8 mg/mouse) with or without ovalbumin (OVA). The pathologic changes in the airway, cytological alteration in bronchoalveolar lavage fluid (BALF), and levels of inflammatory cytokines/chemokines in BALF, and OVA-specific IgE and IgG1 antibodies in serum were measured in the treated CD-1 mice.

Results: Four-time co-exposure to OVA and ASD aggravates allergic airway inflammation along with Th2-cytokine IL-13 and eosinophil-relevant cytokine/chemokines IL-5, Eotaxin and MCP-3 in BALF, and fibrous thickening of the subepithelial layer in the airway. On the other hand, eight-time co-exposure attenuates these changes along with a significant increase of TGF-β1 in BALF. Adjuvant effects of ASD toward IgG1 and IgE production in sera were, however, still seen in the eight-time co-exposure.

Conclusions: These results indicate that the immune responses in airways are exacerbated by four-time co-exposure to ASD with OVA, but that there is a shift to suppressive responses in eight-time co-exposure, suggesting that the responses are caused by TGF-β1-related immune tolerance.