Use of long term dermal sensitization followed by intratracheal challenge method to identify low-dose chemical-induced respiratory allergic responses in mice.
The inhalation of many types of chemicals, including pesticides, perfumes, and other low-molecular weight chemicals, is a leading cause of allergic respiratory diseases. We attempted to develop a new test protocol to detect environmental chemical-related respiratory hypersensitivity at low and weakly immunogenic doses. We used long-term dermal sensitization followed by a low-dose intratracheal challenge to evaluate sensitization by the well-known respiratory sensitizers trimellitic anhydride (TMA) and toluene diisocyanate (TDI) and the contact sensitizer 2,4-dinitrochlorobenzene (DNCB). After topically sensitizing BALB/c mice (9 times in 3 weeks) and challenging them intratracheally with TMA, TDI, or DNCB, we assayed differential cell counts and chemokine levels in bronchoalveolar lavage fluid (BALF); lymphocyte counts, surface antigen expression of B cells, and local cytokine production in lung-associated lymph nodes (LNs); and antigen-specific IgE levels in serum and BALF. TMA induced marked increases in antigen-specific IgE levels in both serum and BALF, proliferation of eosinophils and chemokines (MCP-1, eotaxin, and MIP-1beta) in BALF, and proliferation of Th2 cytokines (interleukin (IL)-4, IL-10, and IL-13) in restimulated LN cells. TDI induced marked increases in levels of cytokines (IL-4, IL-10, IL-13, and IFN-gamma) produced by restimulated LN cells. In contrast, DNCB treatment yielded, at most, small, nonsignificant increases in all parameters. Our protocol thus detected respiratory allergic responses to low-molecular weight chemicals and may be useful for detecting environmental chemical-related respiratory allergy.
Fukuyama
Tomoki
T
Institute of Environmental Toxicology, Ibaraki 303-0043, Japan. fukuyama@iet.or.jp
Ueda
Hideo
H
Hayashi
Koichi
K
Tajima
Yukari
Y
Shuto
Yasufumi
Y
Saito
Toru R
TR
Harada
Takanori
T
Kosaka
Tadashi
T
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D004137:Dinitrochlorobenzene / Q000276:immunology / Q000633:toxicity; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004785:Environmental Pollutants / Q000276:immunology / Q000633:toxicity*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010796:Phthalic Anhydrides / Q000276:immunology / Q000633:toxicity; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology; D014051:Toluene 2,4-Diisocyanate / Q000276:immunology / Q000633:toxicity; D014132:Trachea / Q000276:immunology
D016207:Cytokines; D004137:Dinitrochlorobenzene; D004785:Environmental Pollutants; D010796:Phthalic Anhydrides; D014051:Toluene 2,4-Diisocyanate; D007073:Immunoglobulin E; C015559:trimellitic anhydride