Research Unit Lung Toxicology, Katholieke Universiteit Leuven, Leuven, Belgium.
PLoS One. 2010 Sep 7;5(9):e12581. doi: 10.1371/journal.pone.0012581.
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 microl). 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 IgG(2a) 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-gamma 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.
The used mouse strain has considerable and variable impacts on different aspects of the asthma phenotype. The human phenotypical characteristics of chemically-induced occupational asthma were best reproduced in Th2-biased mice and in particular in BALB/c mice.
职业性哮喘的发生是环境因素与个体易感性相互作用的结果。我们评估了使用不同品系小鼠对化学诱导性哮喘模型的影响。
方法/主要发现：7 种不同品系（BALB/c、BP/2、A/J、C57Bl/6、DBA/2、CBA 和 AKR）雄性小鼠于第 1 天和第 8 天，双侧耳背部皮肤涂抹甲苯二异氰酸酯（TDI）（0.3%）或溶剂（丙酮/橄榄油，2:3）（20 μl）。第 15 天，经口给予 TDI（0.01%）或 AOO（1:4）。检测气道对乙酰甲胆碱的反应性、支气管肺泡灌洗液（BAL）中的总细胞和分类细胞计数、总血清 IgE 和 IgG(2a)水平，以及耳淋巴结中的淋巴细胞亚群和 ConA 刺激的淋巴细胞体外细胞因子释放情况。在 TDI 致敏和激发的小鼠中，气道高反应性仅见于 BALB/c、BP/2、A/J 和 AKR 小鼠；BALB/c 小鼠气道炎症最为明显；BALB/c、BP/2、A/J 和 CBA 小鼠耳淋巴结中 T 辅助细胞（CD4(+））、T 激活细胞（CD4(+)CD25(+））、T 细胞毒性细胞（CD8(+））和 B 淋巴细胞（CD19(+））数量增加；BALB/c、BP/2、A/J、C57Bl/6 和 CBA 小鼠淋巴细胞经 ConA 培养后上清液中 IL-4、IL-10、IL-13 和 IFN-gamma 浓度升高，同时总血清 IgE 增加。
所用小鼠品系对哮喘表型的不同方面有显著且可变的影响。化学诱导性职业性哮喘的人类表型特征在 Th2 偏向型小鼠中得到了最好的再现，尤其是在 BALB/c 小鼠中。
