Expression of respiratory mucins in fatal status asthmaticus and mild asthma

Expression of respiratory mucins in fatal status asthmaticus and mild asthma
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DOI:
10.1046/j.1365-2559.2002.01378.x
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发表时间:
2002-04-01
期刊:
影响因子:
6.4
通讯作者:
Chung, KF
Chung, KF
中科院分区:
医学2区
文献类型:
--
作者:
Groneberg, DA;Eynott, PR;Chung, KF

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目的:哮喘患者气道的特点是以t细胞和嗜酸性粒细胞为主的慢性炎症改变,气道重塑伴杯状细胞化生和粘膜下腺增生。粘液分泌过多通常是一个显著特征,特别是在哮喘状态下。气道痰液基质由高分子糖蛋白和粘蛋白组成。本研究研究了致死性哮喘组织和轻度哮喘患者支气管活检组织中主要凝胶形成粘蛋白MUC5AC和MUC5B的表达和分布。还研究了吸入皮质类固醇对这些粘蛋白表达的影响。方法与结果:分别用MUC5AC和MUC5B特异性多克隆抗体和MUC5B单克隆抗体对哮喘死亡患者(n = 5)和轻度哮喘死亡患者(n = 4)的肺组织和气道粘膜活检组织进行染色。在致死性哮喘患者的组织中,MUC5AC免疫组化结果显示,位于上皮表面衬里和腺管的杯状细胞大量染色。MUC5B免疫反应仅限于粘膜下腺的黏液细胞和上皮细胞。轻度哮喘患者气道管腔内可见大量MUC5B阳性细胞外粘液,但MUC5AC阳性细胞外粘液未见。轻度哮喘患者腺体分泌管的颈部和邻近上皮的。轻度哮喘患者吸入类固醇治疗前后支气管活检MUC5AC和MUC5B的分布相似。结论:在不同哮喘状态下,MUC5AC和MUC5B的表达与正常气道具有相似的分布。分布不受局部皮质类固醇治疗的影响。
Aims: The airways of patients with asthma are characterized by chronic inflammatory changes comprising mainly T-cells and eosinophils, and airway remodelling with goblet cell metaplasia and submucosal gland hyperplasia. Mucus hypersecretion is often a marked feature, particularly in status asthmaticus. The matrix of airway sputum consists of high molecular glycoproteins and mucins. In this study, the expression and distribution of the major gelforming mucins MUC5AC and MUC5B were studied in fatal status asthmaticus tissues and bronchial biopsies of mild asthmatic patients. The effect of inhaled corticosteroids on the expression of these mucins was also investigated.Methods and results: Polyclonal antibodies specific for MUC5AC and MUC5B, and a monoclonal antibody for MUC5B were used to stain lung tissues and airway mucosal biopsies obtained from patients who died of status asthmaticus (n = 5) and from mild asthmatics (n = 4), respectively. Immunohistochemistry for MUC5AC revealed abundant staining of goblet cells situated in the epithelial surface lining and glandular ducts of tissues from patients with fatal asthma. MUC5B immunoreactivity was restricted to mucous cells of submucosal glands and to epithelial cells. In mild asthmatics, large amounts of MUC5B, but not MUC5AC, positive extracellular mucus was found in the airway lumen as plugs. adjacent to the epithelial lining and in the necks of glandular secretory ducts of mild asthmatics. The distribution of MUC5AC and MUC5B in bronchial biopsies of mild asthmatics was similar before and after inhaled steroid treatment.Conclusions: The expression of MUC5AC and MUC5B shares a similar distribution to normal airways in different states of asthma. The distribution is not affected by topical corticosteroid therapy.