Laboratory Medicine, Lund University Hospital, Lund, Sweden.
Clin Exp Allergy. 2014 Feb;44(2):173-83. doi: 10.1111/cea.12255.
Primary lysis of eosinophils liberates free eosinophil granules (FEGs) releasing toxic proteins in association with bronchial epithelial injury repair. Eosinophil lysis may be significantly pathogenic. Bronchial mucosal FEGs are associated with uncontrolled asthma, severe asthma, aspirin-sensitive asthma, and lethal asthma. FEGs in the bronchial wall may characterize severe asthma without sputum eosinophilia. Excessive numbers of sputum FEGs occur in severe exacerbations of asthma and are reduced along with clinical improvement. Occurrence of FEGs affects interpretation of other sputum biomarkers including numbers of eosinophils, ECP, and eosinophil-stained macrophages. Thus, eosinophil lysis produces FEGs as bronchial biomarkers of severe asthma. Blood eosinophils in severe asthma seem primed exhibiting a propensity to lyse that is greater the more severe the asthma. Proclivity of blood eosinophils to lyse also distinguished three levels of severity among children with exacerbations of asthma. Numerous FEGs releasing toxic proteins occur in association with grave derangement and shedding of epithelium in severe asthma. Subepithelial FEGs correlate negatively with intact bronchial epithelium in clinically uncontrolled asthma. Significant correlations between sputum ECP, Creola bodies, and severity of asthma exacerbations have also been demonstrated. Hence, eosinophil lysis apparently causes epithelial desquamation in severe asthma. Exaggerated epithelial repair in turn would contribute to inflammatory and remodelling features of severe asthma. Perseverance of FEGs together with maintained disease activity, despite treatment with 'eosinophil-depleting' steroids and anti-IL5 biologicals, agrees with the possibility that eosinophil lysis is worthy target for novel anti-asthma drugs. Priming and lysis of eosinophils, and protein release from FEGs, are regulated and can be targeted. Eosinophil lysis and FEGs belong to the disease picture of severe asthma and need consideration in asthma studies concerned with phenotypes, biomarkers, roles of epithelial injury/repair, and targeting novel drugs.
嗜酸性粒细胞的原发性溶解会释放游离嗜酸性粒细胞颗粒 (FEGs)，这些颗粒与支气管上皮损伤修复有关，并释放有毒蛋白。嗜酸性粒细胞的溶解可能具有显著的致病性。支气管黏膜 FEGs 与未控制的哮喘、严重哮喘、阿司匹林敏感的哮喘和致命性哮喘有关。支气管壁中的 FEGs 可能是严重哮喘但无痰嗜酸性粒细胞增多的特征。在哮喘严重恶化时，痰 FEGs 数量过多，并随着临床改善而减少。FEGs 的发生会影响对其他痰生物标志物（包括嗜酸性粒细胞、ECP 和嗜酸性粒细胞染色的巨噬细胞）的解读。因此，嗜酸性粒细胞的溶解产生了 FEGs，作为严重哮喘的支气管生物标志物。严重哮喘患者的血液嗜酸性粒细胞似乎已经准备好发生溶解，而且哮喘越严重，这种倾向就越大。血液嗜酸性粒细胞的溶解倾向也区分了哮喘加重患儿的三个严重程度级别。在严重哮喘中，大量释放有毒蛋白的 FEGs 与严重的上皮紊乱和脱落有关。在未控制的临床哮喘中，亚上皮 FEGs 与完整的支气管上皮呈负相关。在哮喘加重中，痰 ECP、Creola 体和哮喘严重程度之间也存在显著相关性。因此，嗜酸性粒细胞的溶解显然会导致严重哮喘中的上皮脱落。反过来，过度的上皮修复将导致严重哮喘的炎症和重塑特征。尽管使用“嗜酸性粒细胞耗竭”类固醇和抗 IL-5 生物制剂进行了治疗，但 FEGs 的持续存在和疾病活动的维持，表明嗜酸性粒细胞的溶解可能是新型抗哮喘药物的一个有价值的靶点。嗜酸性粒细胞的致敏和溶解以及 FEGs 中蛋白质的释放是受调控的，可以作为靶向治疗的目标。嗜酸性粒细胞的溶解和 FEGs 属于严重哮喘的疾病特征，需要在关注表型、生物标志物、上皮损伤/修复作用以及靶向新型药物的哮喘研究中加以考虑。
