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胶原受体α1β1和α2β1整合素在支气管哮喘患者血液嗜酸性粒细胞上的表达增加。

Increased expression of collagen receptors: alpha1beta1 and alpha2beta1 integrins on blood eosinophils in bronchial asthma.

作者信息

Bazan-Socha S, Bukiej A, Pulka G, Marcinkiewicz C, Musial J

机构信息

Department of Medicine, Jagiellonian University School of Medicine, Krakow, Poland.

出版信息

Clin Exp Allergy. 2006 Sep;36(9):1184-91. doi: 10.1111/j.1365-2222.2006.02540.x.

Abstract

BACKGROUND

Eosinophils are one of the major effector cells in bronchial asthma. Their infiltration of airways correlates with the asthma severity. Recruitment and activation of eosinophils are partially mediated by integrins alpha4beta1 and alpha4beta7. Collagens type I and IV constitute important components of extracellular matrix and vascular basement membrane, respectively. Therefore, collagen-binding integrins (alpha1beta1 and alpha2beta1) may also play a role in eosinophil lung infiltration.

OBJECTIVE

To evaluate the possible presence of alpha1beta1 and alpha2beta1 integrins on peripheral blood eosinophils from asthmatic subjects.

METHODS

Collagen receptors were studied on eosinophils separated by immunomagnetic CD16-negative method from healthy donors (n=13) and patients with moderate persistent atopic bronchial asthma (n=15). Surface receptor identification was performed by flow cytometry and cell adhesion assay.

RESULTS

Eosinophils isolated from the patients showed increased expression of both alpha1beta1 and alpha2beta1 integrins as compared with healthy controls. Moreover, adhesive function of eosinophils to collagen type IV was inhibited by snake venom disintegrins: viperistatin and obtustatin. These disintegrins contain KTS active motif and are specific inhibitors of alpha1beta1 integrin.

CONCLUSION

We demonstrated for the first time that collagen receptors: alpha1beta1 and alpha2beta1 integrins are overexpressed on the surface of peripheral blood eosinophils of asthmatic subjects. Further studies may reveal potential application of KTS-disintegrins or their structural analogs for therapy of bronchial asthma.

摘要

背景

嗜酸性粒细胞是支气管哮喘的主要效应细胞之一。它们在气道中的浸润与哮喘严重程度相关。嗜酸性粒细胞的募集和激活部分由整合素α4β1和α4β7介导。I型和IV型胶原分别构成细胞外基质和血管基底膜的重要成分。因此,胶原结合整合素(α1β1和α2β1)可能也在嗜酸性粒细胞肺浸润中发挥作用。

目的

评估哮喘患者外周血嗜酸性粒细胞上α1β1和α2β1整合素的可能存在情况。

方法

采用免疫磁珠法分离健康供者(n = 13)和中度持续性特应性支气管哮喘患者(n = 15)的嗜酸性粒细胞,研究其胶原受体。通过流式细胞术和细胞黏附试验进行表面受体鉴定。

结果

与健康对照相比,从患者分离出的嗜酸性粒细胞显示α1β1和α2β1整合素的表达均增加。此外,蛇毒解整合素:蝰蛇抑制素和钝吻抑制素可抑制嗜酸性粒细胞与IV型胶原的黏附功能。这些解整合素含有KTS活性基序,是α1β1整合素的特异性抑制剂。

结论

我们首次证明胶原受体:α1β1和α2β1整合素在哮喘患者外周血嗜酸性粒细胞表面过度表达。进一步研究可能揭示KTS - 解整合素或其结构类似物在支气管哮喘治疗中的潜在应用。

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