Shinagawa Kazuhiko, Kojima Masami
Pharmacology Lab, Kissei Pharmaceutical Co. Ltd., Minamiazumi, Nagano, Japan.
Am J Respir Crit Care Med. 2003 Oct 15;168(8):959-67. doi: 10.1164/rccm.200210-1188OC. Epub 2003 Jul 11.
We found that continuous eosinophilic inflammation after repeated antigen instillation into the nose was observed only in A/J mice, not in three other strains. Histologic analysis of tissues from A/J mice revealed features typical of airway remodeling, i.e., airway wall thickening and increased collagen depositions were observed after 12 weeks' antigen exposure. Persistent airway hyperresponsiveness (AHR) was observed in chronically antigen-exposed A/J mice. Eosinophilic inflammation, collagen deposition, and airway wall thickening were all less marked in BALB/c mice than in A/J mice, and no AHR was observed in the former strain. In C57BL/6 and C3H/HeJ mice, eosinophilic inflammation, airway wall thickening, and AHR were not observed at all, although slightly increased collagen deposition was observed. Thus, we found that these changes were strain-dependent. On the other hand, in A/J mice inhalational antigen challenge after ovalbumin/alum immunization led only to a transient increase in eosinophils and to less airway wall thickening, indicating the importance of the protocol used. Use of A/J mice and giving antigen by instillation via the nose is to be recommended for studies of the mechanisms underlying asthma. In particular, useful qualitative and quantitative information relating to the structural and histologic changes in the lungs may be obtainable using this model.
我们发现,仅在A/J小鼠中观察到反复向鼻腔内滴注抗原后出现持续性嗜酸性粒细胞炎症,而在其他三种品系的小鼠中未观察到。对A/J小鼠组织的组织学分析显示出气道重塑的典型特征,即抗原暴露12周后观察到气道壁增厚和胶原沉积增加。在长期暴露于抗原的A/J小鼠中观察到持续性气道高反应性(AHR)。BALB/c小鼠中的嗜酸性粒细胞炎症、胶原沉积和气道壁增厚均不如A/J小鼠明显,且在前一品系中未观察到AHR。在C57BL/6和C3H/HeJ小鼠中,虽然观察到胶原沉积略有增加,但未观察到嗜酸性粒细胞炎症、气道壁增厚和AHR。因此,我们发现这些变化具有品系依赖性。另一方面,在A/J小鼠中,卵清蛋白/明矾免疫后吸入抗原激发仅导致嗜酸性粒细胞短暂增加和气道壁增厚减轻,表明所用方案的重要性。对于哮喘潜在机制的研究,建议使用A/J小鼠并通过鼻腔滴注给予抗原。特别是,使用该模型可能获得与肺部结构和组织学变化相关的有用定性和定量信息。