Alveolar macrophages from subjects with chronic obstructive pulmonary disease are deficient in their ability to phagocytose apoptotic airway epithelial cells
Alveolar macrophages from subjects with chronic obstructive pulmonary disease are deficient in their ability to phagocytose apoptotic airway epithelial cells
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DOI：
10.1046/j.1440-1711.2003.t01-1-01170.x
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发表时间：
2003-08-01
影响因子：
4
通讯作者：
Holmes, M
中科院分区：
文献类型：
--
作者：
Hodge, S;Hodge, G;Holmes, M
慢性阻塞性肺疾病是一种高度流行的复杂疾病，通常由吸烟引起。它造成严重的发病率和死亡率，每年使全球社会损失数十亿美元。虽然慢性炎症，细胞外基质破坏和气道上皮细胞凋亡增加在慢性阻塞性肺疾病的报告，了解疾病的基本发病机制是有限的，没有有效的治疗。我们推测慢性阻塞性肺疾病患者气道上皮细胞凋亡的累积可能是由于肺泡巨噬细胞吞噬清除功能缺陷所致。以前没有使用生理学相关的凋亡气道上皮细胞作为吞噬靶点来研究慢性阻塞性肺疾病中肺泡巨噬细胞的吞噬能力。我们开发了一种吞噬试验，其中培养的16 HBE气道上皮细胞用紫外线辐射诱导凋亡，并用mitotracker绿色染色。肺泡巨噬细胞从支气管肺泡灌洗8个控制和6个慢性阻塞性肺疾病的主题进行了分析后，1.5小时的孵育与凋亡的气道上皮细胞，然后用巨噬细胞标记物抗CD 33染色。CD 33 +/mitotracker绿色+事件（即，已吞噬凋亡气道上皮细胞的肺泡巨噬细胞）使用流式细胞术进行分析。平行研究了聚苯乙烯微珠的吞噬作用。与对照组相比，慢性阻塞性肺疾病受试者的肺泡巨噬细胞摄取凋亡气道上皮细胞的比例显著降低（慢性阻塞性肺疾病组为11.6 +/- 4.1%，对照组为25.6 +/- 9.2%）。重要的是，使用聚苯乙烯珠没有观察到这种缺陷，这表明未能解决慢性阻塞性肺疾病中的上皮损伤可能至少部分是由于肺泡巨噬细胞摄取凋亡气道上皮细胞的吞噬能力的特定缺陷。
Chronic obstructive pulmonary disease is a highly prevalent, complex disease, usually caused by cigarette smoke. It causes serious morbidity and mortality and costs the global community billions of dollars per year. While chronic inflammation, extracellular matrix destruction and increased airway epithelial cell apoptosis are reported in chronic obstructive pulmonary disease, the understanding of the basic pathogenesis of the disease is limited and there are no effective treatments. We hypothesized that the accumulation of apoptotic airway epithelial cells chronic obstructive pulmonary disease in could be due to defective phagocytic clearance by alveolar macrophages. There have been no previous studies of the phagocytic capacity of alveolar macrophages in chronic obstructive pulmonary disease using physiologically relevant apoptotic airway epithelial cells as phagocytic targets. We developed a phagocytosis assay whereby cultured 16HBE airway epithelial cells were induced to apoptosis with ultraviolet radiation and stained with mitotracker green. Alveolar macrophages from bronchoalveolar lavage from eight control and six chronic obstructive pulmonary disease subjects were analysed following 1.5 h incubation with apoptotic airway epithelial cells, then staining with macrophage marker anti CD33. CD33+/mitotracker green + events (i.e., alveolar macrophages which had phagocytosed apoptotic airway epithelial cells) were analysed using flow cytometry. Phagocytosis of polystyrene microbeads was investigated in parallel. A significantly reduced proportion of alveolar macrophages from chronic obstructive pulmonary disease subjects ingested apoptotic airway epithelial cells compared with controls (11.6 +/- 4.1% for chronic obstructive pulmonary disease versus 25.6 +/- 9.2% for control group). Importantly, the deficiency was not observed using polystyrene beads, suggesting that the failure to resolve epithelial damage in chronic obstructive pulmonary disease may result, at least partially, from specific defects in phagocytic ability of alveolar macrophages to ingest apoptotic airway epithelial cells.