Denzler K L, Farmer S C, Crosby J R, Borchers M, Cieslewicz G, Larson K A, Cormier-Regard S, Lee N A, Lee J J
Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, Samuel C. Johnson Medical Research Building, Scottsdale, AZ 85259, USA.
J Immunol. 2000 Nov 15;165(10):5509-17. doi: 10.4049/jimmunol.165.10.5509.
The relationship between eosinophils and the development of Ag-induced pulmonary pathologies, including airway hyper-responsiveness, was investigated using mice deficient for the secondary granule component, major basic protein-1 (mMBP-1). The loss of mMBP-1 had no effect on OVA-induced airway histopathologies or inflammatory cell recruitment. Lung function measurements of knockout mice demonstrated a generalized hyporeactivity to methacholine-induced airflow changes (relative to wild type); however, this baseline phenotype was observable only with methacholine; no relative airflow changes were observed in response to another nonspecific stimulus (serotonin). Moreover, OVA sensitization/aerosol challenge of wild-type and mMBP-1(-/-) mice resulted in identical dose-response changes to either methacholine or serotonin. Thus, the airway hyper-responsiveness in murine models of asthma occurs in the absence of mMBP-1.
利用缺乏二级颗粒成分主要碱性蛋白-1(mMBP-1)的小鼠,研究了嗜酸性粒细胞与变应原诱导的肺部病变(包括气道高反应性)发展之间的关系。mMBP-1的缺失对卵清蛋白诱导的气道组织病理学或炎症细胞募集没有影响。基因敲除小鼠的肺功能测量显示,对乙酰甲胆碱诱导的气流变化普遍反应低下(相对于野生型);然而,这种基线表型仅在乙酰甲胆碱刺激下可观察到;对另一种非特异性刺激(血清素)未观察到相对气流变化。此外,野生型和mMBP-1(-/-)小鼠的卵清蛋白致敏/气雾剂激发对乙酰甲胆碱或血清素产生相同的剂量反应变化。因此,哮喘小鼠模型中的气道高反应性在没有mMBP-1的情况下也会发生。