choice of mouse strain influences the outcome in a mouse model of chemical-induced asthma选择鼠标应变结果chemical-induced哮喘小鼠模型的影响.pdfVIP

Choice of Mouse Strain Influences the Outcome in a Mouse Model of Chemical-Induced Asthma Vanessa De Vooght.*, Jeroen A. J. Vanoirbeek., Katrien Luyts, Steven Haenen, Benoit Nemery, Peter H. M. Hoet Research Unit Lung Toxicology, Katholieke Universiteit Leuven, Leuven, Belgium Abstract Background: The development of occupational asthma is the result of interactions between environmental factors and individual susceptibility. We assessed how our model of chemical-induced asthma is influenced by using different mouse strains. Methodology/Principal Findings: On days 1 and 8, male mice of 7 different strains (BALB/c, BP/2, A/J, C57Bl/6, DBA/2, CBA and AKR) were dermally treated with toluene-2,4-diisocyanate (TDI) (0.3%) or vehicle (acetone/olive oil, AOO, 2:3) on each ear (20 ml). On day 15, they received an oropharyngeal instillation of TDI (0.01%) or AOO (1:4). Airway reactivity to methacholine, total and differential cell counts in bronchoalveolar lavage (BAL) and total serum IgE and IgG2a levels were measured. Lymphocyte subpopulations in auricular lymph nodes and in vitro release of cytokines by ConA stimulated lymphocytes were assessed. In TDI-sensitized and challenged mice, airway hyper-reactivity was only observed in BALB/c, BP/ 2, A/J and AKR mice; airway inflammation was most pronounced in BALB/c mice; numbers of T-helper (CD4+), T-activated (CD4+ + + + CD25 ), T-cytotoxic (CD8 ) and B- lymphocytes (CD19 ) were increased in the auricular lymph nodes of BALB/c, BP/2, A/J and CBA mice; elevated concentrations of IL-4, IL-10, IL-13 and IFN-c were detected in supernatant of lymphocytes from BALB/c, BP/2, A/J, C57Bl/6 and CBA mice cultured with concanavaline A, along with an increase in total serum IgE. Conclusion: The used mouse