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粒细胞巨噬细胞集落刺激因子是增强哮喘气道中嗜酸性粒细胞存活率的主要细胞因子。

Granulocyte macrophage colony-stimulating factor is the main cytokine enhancing survival of eosinophils in asthmatic airways.

作者信息

Park C S, Choi Y S, Ki S Y, Moon S H, Jeong S W, Uh S T, Kim Y H

机构信息

Dept of Internal Medicine, Soonchunhyang University Hospital, Seoul, Korea.

出版信息

Eur Respir J. 1998 Oct;12(4):872-8. doi: 10.1183/09031936.98.12040872.

DOI:10.1183/09031936.98.12040872
PMID:9817161
Abstract

Interleukin (IL)-3, IL-5 and granulocyte macrophage colony-stimulating factor (GM-CSF) prolong the survival of eosinophils, which are conspicuous in asthmatic airways, but it is still controversial which one plays a major role in enhancing the survival of eosinophils in asthmatic airways. The role of these cytokines in airway eosinophilia was investigated using bronchoalveolar lavage (BAL) fluids from 11 symptomatic and nine asymptomatic patients with asthma and eight normal subjects. Eosinophil survival-enhancing activity (ESEA) was measured by a numerical change in viable eosinophils isolated from the peripheral blood of atopic patients and cultured with BAL fluids. ESEA was characterized by neutralization with antibodies to IL-3, IL-5 and/or GM-CSF. The differential count of BAL cells was achieved using Diff-Quik stain. T-cell subsets and activated T-cells were analysed by flow cytometry with dual stain using monoclonal antibodies to CD3, CD4, CD8 and CD25. ESEA was detected in eight of 11 BAL fluids of symptomatic asthma, but not in those of normal controls or asymptomatic asthmatics. In six symptomatic asthmatics, the mean percentage of inhibition in ESEA by anti-GM-CSF was higher than that of anti-IL-5 as well as anti-IL-3 (p<0.05). A mixture of antibodies to IL-3, IL-5 and GM-CSF totally inhibited the ESEA in four cases. The ESEA correlated with the percentage of eosinophils (p<0.05) and that of CD25(+)CD4 lymphocytes (p<0.05) of BAL cells. In conclusion, granulocyte macrophage colony-stimulating factor, rather than interleukin-3 or -5, is associated with eosinophil survival-enhancing activity inside the airways of symptomatic asthmatics. The activation of CD4 lymphocytes is related to the elevation of such activity.

摘要

白细胞介素(IL)-3、IL-5和粒细胞巨噬细胞集落刺激因子(GM-CSF)可延长嗜酸性粒细胞的存活时间,嗜酸性粒细胞在哮喘气道中很明显,但在增强哮喘气道中嗜酸性粒细胞的存活方面哪一种因子起主要作用仍存在争议。使用11例有症状的哮喘患者、9例无症状的哮喘患者和8名正常受试者的支气管肺泡灌洗(BAL)液,研究了这些细胞因子在气道嗜酸性粒细胞增多症中的作用。通过从特应性患者外周血中分离并与BAL液一起培养的活嗜酸性粒细胞的数量变化来测量嗜酸性粒细胞存活增强活性(ESEA)。ESEA的特征是用抗IL-3、IL-5和/或GM-CSF抗体进行中和。使用Diff-Quik染色对BAL细胞进行分类计数。通过使用针对CD3、CD4、CD8和CD25的单克隆抗体进行双色流式细胞术分析T细胞亚群和活化的T细胞。在11例有症状哮喘患者的BAL液中,有8例检测到ESEA,但在正常对照或无症状哮喘患者的BAL液中未检测到。在6例有症状的哮喘患者中,抗GM-CSF对ESEA的平均抑制百分比高于抗IL-5和抗IL-3(p<0.05)。抗IL-3、IL-5和GM-CSF的抗体混合物在4例中完全抑制了ESEA。ESEA与BAL细胞中嗜酸性粒细胞的百分比(p<0.05)和CD25(+)CD4淋巴细胞的百分比(p<0.05)相关。总之,粒细胞巨噬细胞集落刺激因子而非白细胞介素-3或-5与有症状哮喘患者气道内的嗜酸性粒细胞存活增强活性有关。CD4淋巴细胞的活化与这种活性的升高有关。

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