Woolley K L, Adelroth E, Woolley M J, Ellis R, Jordana M, O'Byrne P M
Dept of Medicine, McMaster University, Hamilton, Canada.
Eur Respir J. 1994 Sep;7(9):1576-84. doi: 10.1183/09031936.94.07091576.
Increasing evidence implicates the eosinophil as an important effector cell in asthma, but little is known regarding its regulation in vivo. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to regulate eosinophil function in vitro. We investigated the in vivo role of eosinophils and GM-CSF in mild asthma. We compared the number and function of eosinophils and the presence of GM-CSF in blood, bronchoalveolar lavage (BAL) and biopsy tissue obtained from eight mild, stable, atopic asthmatics and 10 nonasthmatics, five of whom were atopic and five nonatopic. Eosinophils were significantly increased in the blood, BAL and biopsy tissue from asthmatics. Activated eosinophils, assessed by immunostaining for the secreted form of eosinophil cationic protein (EG2), were also increased in asthmatic BAL cells and biopsy tissue. Significant increases in GM-CSF in BAL cells and biopsy tissue from asthmatics were also evident. Significant positive correlations existed between GM-CSF in BAL and EG2, and GM-CSF in biopsy tissue and BAL and biopsy eosinophils. Airway responsiveness was also significantly positively correlated with eosinophil number and activation, and with GM-CSF. These results demonstrate that there are increased numbers of activated eosinophils and GM-CSF is increased in patients with mild asthma. Furthermore, GM-CSF is correlated with eosinophil number and function in vivo and these indices are significantly correlated with airway function. These findings emphasize the importance of eosinophils, potentially regulated in vivo by GM-CSF, in contributing to the disordered airway function evident even in mild asthma.
越来越多的证据表明嗜酸性粒细胞是哮喘中的重要效应细胞,但对其在体内的调节知之甚少。粒细胞-巨噬细胞集落刺激因子(GM-CSF)已被证明在体外可调节嗜酸性粒细胞功能。我们研究了嗜酸性粒细胞和GM-CSF在轻度哮喘中的体内作用。我们比较了从8名轻度、稳定、特应性哮喘患者和10名非哮喘患者(其中5名特应性和5名非特应性)获取的血液、支气管肺泡灌洗(BAL)液和活检组织中嗜酸性粒细胞的数量和功能以及GM-CSF的存在情况。哮喘患者的血液、BAL液和活检组织中的嗜酸性粒细胞显著增加。通过对嗜酸性粒细胞阳离子蛋白分泌形式(EG2)进行免疫染色评估的活化嗜酸性粒细胞,在哮喘患者的BAL细胞和活检组织中也增加。哮喘患者的BAL细胞和活检组织中GM-CSF也显著增加。BAL液中的GM-CSF与EG2之间、活检组织中的GM-CSF与BAL及活检嗜酸性粒细胞之间存在显著正相关。气道反应性也与嗜酸性粒细胞数量和活化以及GM-CSF显著正相关。这些结果表明,轻度哮喘患者中活化嗜酸性粒细胞数量增加且GM-CSF升高。此外,GM-CSF在体内与嗜酸性粒细胞数量和功能相关,且这些指标与气道功能显著相关。这些发现强调了嗜酸性粒细胞的重要性,其可能在体内受GM-CSF调节,对即使在轻度哮喘中也明显存在的气道功能紊乱起作用。