Impaired macrophage phagocytosis in non-eosinophilic asthma
Impaired macrophage phagocytosis in non-eosinophilic asthma
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DOI：
10.1111/j.1365-2222.2012.04075.x
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发表时间：
2013-01-01
影响因子：
6.1
通讯作者：
Hodge, S.
中科院分区：
文献类型：
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作者：
Simpson, J. L.;Gibson, P. G.;Hodge, S.
背景许多非嗜酸性粒细胞性哮喘患者气道内中性粒细胞数量增加。对这种慢性炎症的解释尚不清楚，但可能是由于肺泡巨噬细胞吞噬凋亡细胞的能力受损（一种称为细胞凋亡的过程），正如我们在慢性阻塞性肺疾病（COPD）中所示。目的探讨诱导痰作为一种非侵入性检测慢性肺疾病患者嗜酸性粒细胞增多症的方法，并比较非嗜酸性粒细胞性哮喘、嗜酸性粒细胞性哮喘和慢性阻塞性肺疾病患者的嗜酸性粒细胞增多症。方法对11例稳定期哮喘患者（嗜酸粒细胞性哮喘20例，非嗜酸粒细胞性哮喘30例）和11例COPD患者进行过敏性皮肤试验、生理盐水激发试验和痰诱导试验。使用二硫苏糖醇分散痰液细胞，并重悬于培养基中。采用流式细胞术测定肺癌衍生的巨噬细胞对凋亡支气管上皮细胞的胞饮作用。结果3例受试者配对痰液和支气管肺泡灌洗液中巨噬细胞的吞噬功能无显著性差异。与嗜酸性粒细胞性哮喘患者[1.17（0.19）]相比，非嗜酸性粒细胞性哮喘患者的胞饮功能显著受损[平均值（SD）0.95（0.24）]，与COPD患者的程度相似[1.04（0.16）]。COPD和非嗜酸性粒细胞哮喘患者的痰液中性粒细胞显著高于嗜酸性粒细胞哮喘患者。结论：诱导痰法是一种可靠的、无创性的方法，可用于研究慢性肺疾病患者的巨噬细胞吞噬功能。非嗜酸性粒细胞性哮喘患者的巨噬细胞吞噬功能受损程度与COPD患者相似，这可能解释了这种哮喘亚型的持续气道嗜酸性粒细胞性和慢性炎症特征。
Background Many patients with non-eosinophilic asthma have increased numbers of neutrophils in the airways. The explanation for this chronic inflammation remains unclear, but may result from an impaired ability of alveolar macrophages to phagocytose apoptotic cells (a process termed efferocytosis), as we have shown in chronic obstructive pulmonary disease (COPD). Objectives To examine induced sputum as a non-invasive technique to characterize efferocytosis in chronic lung diseases and to compare efferocytosis in patients with non-eosinophilic asthma, eosinophilic asthma and COPD. Methods Participants with stable asthma (20 with eosinophilic and 30 with non-eosinophilic) and COPD (n = 11) underwent clinical assessment including allergy skin tests, saline challenge and sputum induction. Sputum cells were dispersed using dithiothreitol and resuspended in culture medium. Efferocytosis of apoptotic bronchial epithelial cells by sputum-derived macrophages was determined using flow cytometry. Results There were no significant differences in efferocytosis between paired sputum and bronchoalveolar lavage macrophages from three subjects. Efferocytosis was significantly impaired in patients with non-eosinophilic asthma [mean (SD) 0.95 (0.24)] compared with eosinophilic asthma [1.17 (0.19)] and to a similar degree as patients with COPD [1.04 (0.16)]. Sputum neutrophils were significantly higher in patients with COPD and non-eosinophilic asthma compared with eosinophilic asthma. Conclusion and Clinical Relevance Induced sputum provides a reliable and non-invasive method for studying macrophage efferocytosis in chronic lung disease. Macrophage efferocytosis is impaired in non-eosinophilic asthma to a similar degree as that in COPD and may explain the persistent airway neutrophilia and chronic inflammation that characterizes this asthma subtype.