Wolyniec W W, De Sanctis G T, Nabozny G, Torcellini C, Haynes N, Joetham A, Gelfand E W, Drazen J M, Noonan T C
Department of Immunological Diseases, Research and Development Center, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut 06877, USA.
Am J Respir Cell Mol Biol. 1998 Jun;18(6):777-85. doi: 10.1165/ajrcmb.18.6.3056.
A murine model of asthma is described in which we examined the role of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of airway reactivity, pulmonary eosinophilia, and inflammation. We sensitized wild-type control [C57BL/6J, (+/+)] and ICAM-1 knockout [C57BL/6J-ICAM-1, (-/-)] mice to ovalbumin (OVA), and challenged them with OVA delivered by aerosol (OVA-OVA) to induce a phenotype consistent with an asthmatic response. Bronchial responsiveness to methacholine and counts of cell numbers and measurements of eosinophil content and cytokine levels in bronchoalveolar lavage fluid (BALF) were significantly attenuated in ICAM-1(-/-) mice as compared with (+/+) mice. We also showed that the absence of ICAM-1 had no significant affects on the production of serum IgE antibody, but did have an effect on ex vivo lymphocyte proliferation. Additionally, immunohistochemistry: (1) revealed increased staining for vascular cell adhesion molecule-1 (VCAM-1) after antigen challenge in the ICAM-1(-/-) mice but not in the ICAM-1(+/+) controls; and (2) confirmed the presence of alternatively spliced forms of ICAM-1 in the lungs of ICAM-1(-/-) mice. Thus, despite the availability of alternate adhesion pathways in ICAM-1(-/-) mice, the absence of ICAM-1 prevented eosinophils from entering the airways. In summary, we found that the ICAM-1 knockout mice exhibited a significantly inhibited response to aerosol antigen challenge for most of the parameters examined, and conclude that ICAM-1 is an important ligand mediating T-cell proliferation in response to antigen, eosinophil migration into the airways, and the development of airway hyperreactivity (AHR) in allergen-sensitized and -challenged mice.
本文描述了一种哮喘小鼠模型，我们在该模型中研究了细胞间黏附分子-1（ICAM-1）在气道反应性、肺嗜酸性粒细胞增多症和炎症发病机制中的作用。我们将野生型对照小鼠[C57BL/6J，（+/+）]和ICAM-1基因敲除小鼠[C57BL/6J-ICAM-1，（-/-）]用卵清蛋白（OVA）致敏，然后通过雾化吸入OVA（OVA-OVA）对它们进行激发，以诱导出与哮喘反应一致的表型。与（+/+）小鼠相比，ICAM-1（-/-）小鼠对乙酰甲胆碱的支气管反应性以及支气管肺泡灌洗液（BALF）中的细胞数量计数、嗜酸性粒细胞含量测量和细胞因子水平均显著减弱。我们还表明，ICAM-1的缺失对血清IgE抗体的产生没有显著影响，但对体外淋巴细胞增殖有影响。此外，免疫组织化学显示：（1）抗原激发后，ICAM-1（-/-）小鼠中血管细胞黏附分子-1（VCAM-1）的染色增加，而ICAM-1（+/+）对照小鼠中未增加；（2）证实ICAM-1（-/-）小鼠肺中存在ICAM-1的可变剪接形式。因此，尽管ICAM-1（-/-）小鼠存在其他黏附途径，但ICAM-1的缺失阻止了嗜酸性粒细胞进入气道。总之，我们发现ICAM-1基因敲除小鼠对雾化抗原激发的大多数检测参数反应明显受到抑制，并得出结论，ICAM-1是介导T细胞对抗原反应性增殖、嗜酸性粒细胞向气道迁移以及变应原致敏和激发小鼠气道高反应性（AHR）发展的重要配体。
