Increased number of glucocorticoid receptor-beta-expressing cells in the airways in fatal asthma.
Increased number of glucocorticoid receptor-beta-expressing cells in the airways in fatal asthma.
复制标题
致命性哮喘气道中表达糖皮质激素受体β的细胞数量增加。
DOI：
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发表时间：
2000
影响因子：
14.2
通讯作者：
Q. Hamid
中科院分区：
文献类型：
--
作者：
P. Christodoulopoulos;D. Leung;M. Elliott;J. Hogg;S. Muro;M. Toda;Sophie Laberge;Q. Hamid
背景
我们最近发现，在激素不敏感的严重哮喘患者中，糖皮质激素受体β（GR β）阳性细胞数量增加。对类固醇不敏感可能是致命性哮喘的一个主要因素;然而，以前没有报道过这样的直接证据。
目的
我们的目的是研究GR β免疫反应性的表达，一种内源性类固醇作用抑制剂，以前与类固醇不敏感性，在气道内的患者谁死于缓慢发作的致命性哮喘，并比较其表达在肺气肿患者和非哮喘受试者死于无关的原因。从7名死于哮喘的患者、6名死于肺气肿的患者和8名死于非肺部疾病的患者中获得了大小气道切片。6例因肺癌切除的轻度哮喘患者的肺切片也作为对照。
方法
用抗生物素蛋白-生物素技术和单克隆CD 3、主要碱性蛋白、CD 68和弹性蛋白酶抗体，用GR β多克隆抗体和碱性磷酸酶-抗碱性磷酸酶技术对组织样本进行免疫细胞化学处理。进行免疫细胞化学以表型GR β免疫反应细胞。检查来自大（>2 mm）和小（<2 mm）气道的组织切片。
结果
与肺气肿和对照组相比，致命性哮喘组GR β免疫反应细胞的数量显著增加（分别为P <0.001和P <0.05）。肺气肿组GR β的表达与对照组相比无显著性差异。与轻度哮喘相比，致死性哮喘患者的GR β免疫反应性也显著升高。GR β在重度哮喘患者小气道和大气道中的表达无显著差异。大多数GR β阳性细胞为T细胞，嗜酸性粒细胞、巨噬细胞和中性粒细胞较少。
结论
本研究的结果支持GR β表达与致命性哮喘的相关性，并建议在急性环境中需要考虑对类固醇治疗无反应的患者使用替代抗炎药。
BACKGROUND
We have recently demonstrated an increased number of glucocorticoid receptor-beta (GRbeta)-positive cells in steroid-insensitive subjects with severe asthma. Insensitivity to steroids may be a major contributing factor in fatal asthma; however, no such direct evidence has been report previously.
OBJECTIVE
Our aims were to investigate the expression of GRbeta immunoreactivity, an endogenous inhibitor of steroid action previously associated with steroid insensitivity, within the airways of patients who died of slow-onset fatal asthma and to compare its expression in patients with emphysema and in nonasthmatic subjects who died of unrelated causes. Sections from airways, both large and small, were obtained from 7 patients who died of asthma, 6 who died from emphysema, and 8 who died from nonpulmonary diseases. Sections from lungs of 6 patients with mild asthma whose lungs were resected for carcinoma were also included as controls.
METHODS
Tissue samples were processed for immunocytochemistry with a polyclonal antibody to GRbeta with use of the avidin-biotin technique and with monoclonal CD3, major basic protein, CD68, and elastase antibodies with the alkaline phosphatase-anti-alkaline phosphatase technique. Sequential immunocytochemistry was performed to phenotype the GRbeta immunoreactive cells. Tissue sections from both large (>2 mm) and small (<2 mm) airways were examined.
RESULTS
There was a significantly greater number of GRbeta immunoreactive cells in fatal asthma compared with emphysema and controls (P <.001 and P <.05, respectively). There was no difference in the expression of GRbeta in emphysema compared with controls. GRbeta immunoreactivity was also significantly higher in fatal asthma compared with mild asthma. The expression of GRbeta in the small airways of patients with severe asthma did not differ significantly from that in the large airways. The majority of GRbeta-positive cells were T cells and to a lesser extent eosinophils, macrophages, and neutrophils.
CONCLUSION
The results of this study support the association of GRbeta expression with fatal asthma and suggest that alternative anti-inflammatory agents need to be considered in the acute setting for patients who are not responding to steroid therapy.
IL-2 和 IL-4 组合可降低糖皮质激素受体结合亲和力和 T 细胞对糖皮质激素的反应。
DOI：
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发表时间：
1993
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kam,JC;Szefler,SJ;Surs,W;Sher,ER;Leung,DY
通讯作者：
Leung,DY
DOI：
10.1164/ajrccm.159.5.9804131
发表时间：
1999-05-01
影响因子：
24.7
作者：
Hamid, QA;Wenzel, SE;Leung, DYM
通讯作者：
Leung, DYM