Louis R, Shute J, Biagi S, Stanciu L, Marrelli F, Tenor H, Hidi R, Djukanović R
Immunopharmacology Group, University of Southampton, United Kingdom.
Am J Respir Crit Care Med. 1997 Feb;155(2):466-72. doi: 10.1164/ajrccm.155.2.9032180.
We have applied the technique of sputum induction by hypertonic saline in asthmatics and nonatopic control subjects to study an array of indices of airway inflammation believed to be relevant to asthma pathogenesis. Compatible with a central role for eosinophils and mast cells in asthma, sputum of asthmatic subjects contained increased numbers of eosinophils and levels of eosinophil cationic protein (ECP) and mast cell tryptase. Eosinophil numbers, and ECP and histamine levels correlated with the degree of methacholine airways responsiveness, and ECP, tryptase, and histamine correlated with raised concentrations of albumin. Using the micro-Boyden chamber technique eosinophil chemotactic activity was identified only in the sputum from asthmatics. The correlation between the raised levels of total IgA, IL-8/IgA complexes, and tryptase and the degree of sputum eosinophilia and ECP levels, suggests possible mechanisms for eosinophil chemotaxis and activation in asthma. Row cytometric analysis of sputum lymphocytes showed an increase in CD4+ T cells and T cells expressing intercellular adhesion molecule-1 (ICAM-1) in asthma which, together with the finding of raised levels of soluble ICAM-1 in the sputum, indicates upregulation of this adhesion molecule. Finally, the proportion of CD16+ natural killer (NK) cells was reduced in the sputum of asthmatics. These observations highlight the importance of the airway inflammation in causing asthma and further confirm the usefulness of sputum induction as a tool in asthma research.
我们已将高渗盐水诱导痰技术应用于哮喘患者和非特应性对照受试者,以研究一系列被认为与哮喘发病机制相关的气道炎症指标。与嗜酸性粒细胞和肥大细胞在哮喘中起核心作用相一致,哮喘患者的痰液中嗜酸性粒细胞数量增加,嗜酸性粒细胞阳离子蛋白(ECP)和肥大细胞类胰蛋白酶水平升高。嗜酸性粒细胞数量、ECP和组胺水平与乙酰甲胆碱气道反应性程度相关,ECP、类胰蛋白酶和组胺与白蛋白浓度升高相关。使用微量博伊登室技术,仅在哮喘患者的痰液中鉴定出嗜酸性粒细胞趋化活性。总IgA、IL-8/IgA复合物和类胰蛋白酶水平升高与痰液嗜酸性粒细胞增多程度和ECP水平之间的相关性,提示了哮喘中嗜酸性粒细胞趋化和活化的可能机制。对痰液淋巴细胞进行流式细胞术分析显示,哮喘患者中CD4 + T细胞和表达细胞间黏附分子-1(ICAM-1)的T细胞增加,这与痰液中可溶性ICAM-1水平升高的发现一起,表明该黏附分子上调。最后,哮喘患者痰液中CD16 +自然杀伤(NK)细胞的比例降低。这些观察结果突出了气道炎症在引发哮喘中的重要性,并进一步证实了诱导痰作为哮喘研究工具的实用性。