Extensive Eosinophil Degranulation and Peroxidase-Mediated Oxidation of Airway Proteins Do Not Occur in a Mouse Ovalbumin-Challenge Model of Pulmonary Inflammation1
Extensive Eosinophil Degranulation and Peroxidase-Mediated Oxidation of Airway Proteins Do Not Occur in a Mouse Ovalbumin-Challenge Model of Pulmonary Inflammation1
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小鼠卵清蛋白激发肺部炎症模型中不会发生广泛的嗜酸性粒细胞脱颗粒和过氧化物酶介导的气道蛋白氧化1
作者：
K. Denzler;M. Borchers;J. Crosby;G. Cieslewicz;E. M. Hines;J. Justice;S. Cormier;K. Lindenberger;Wei;Weijia Wu;Stanley L Hazen;G. Gleich;James J. Lee;N. Lee
哮喘患者肺部嗜酸性粒细胞效应功能的范式总是取决于在一个统称为脱颗粒的过程中从次级颗粒释放的阳离子蛋白所介导的活动。在这项研究中，我们培育了缺乏嗜酸性粒细胞过氧化物酶（EPO）的基因敲除小鼠，以评估这种丰富的次级颗粒蛋白在卵清蛋白（OVA）激发模型中的作用。EPO的缺失对小鼠中OVA诱导的病理发展没有影响。这些基因敲除动物缺乏表型后果的情况不仅限于肺组织病理学和气道变化，因为EPO缺陷动物在用甲基胆碱激发后也表现出OVA诱导的气道高反应性。此外，从OVA处理的野生型小鼠支气管肺泡灌洗液中回收的EPO介导的蛋白质氧化损伤（例如，酪氨酸残基的溴化）不到从哮喘患者支气管肺泡灌洗液中观察到的水平的10%。这些数据表明，EPO的活性对小鼠过敏性肺部病理的发展无关紧要，并表明在该模型中募集到肺部的嗜酸性粒细胞的脱颗粒程度与在哮喘患者中观察到的情况不可比。
Paradigms of eosinophil effector function in the lungs of asthma patients invariably depend on activities mediated by cationic proteins released from secondary granules during a process collectively referred to as degranulation. In this study, we generated knockout mice deficient for eosinophil peroxidase (EPO) to assess the role(s) of this abundant secondary granule protein in an OVA-challenge model. The loss of EPO had no effect on the development of OVA-induced pathologies in the mouse. The absence of phenotypic consequences in these knockout animals extended beyond pulmonary histopathologies and airway changes, as EPO-deficient animals also displayed OVA-induced airway hyperresponsiveness after provocation with methacholine. In addition, EPO-mediated oxidative damage of proteins (e.g., bromination of tyrosine residues) recovered in bronchoalveolar lavage from OVA-treated wild-type mice was <10% of the levels observed in bronchoalveolar lavage recovered from asthma patients. These data demonstrate that EPO activities are inconsequential to the development of allergic pulmonary pathologies in the mouse and suggest that degranulation of eosinophils recruited to the lung in this model does not occur at levels comparable to those observed in humans with asthma.
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影响因子：
7.8
作者：
DeKruyff, R H;Rizzo, L V;Umetsu, D T
通讯作者：
Umetsu, D T
DOI：
10.1164/ajrccm.156.3.9606031
发表时间：
1997-09-01
影响因子：
24.7
作者：
Hamelmann, E;Schwarze, J;Gelfand, EW
通讯作者：
Gelfand, EW
影响因子：
15.9
作者：
Shi, HZ;Humbles, A;Weller, PF
通讯作者：
Weller, PF
嗜酸性粒细胞颗粒蛋白体外杀死彭亨丝虫和马来丝虫的微丝蚴。
DOI：
--
发表时间：
1990
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hamann,KJ;Gleich,GJ;Checkel,JL;Loegering,DA;McCall,JW;Barker,RL
通讯作者：
Barker,RL
嗜酸性粒细胞和嗜酸性粒细胞条件培养基中嗜酸性粒细胞过氧化物酶活性的动力学测定。
影响因子：
2.2
作者：
White,SR;Kulp,GV;Spaethe,SM;VanAlstyne,E;Leff,AR
通讯作者：
Leff,AR