Azithromycin increases phagocytosis of apoptotic bronchial epithelial cells by alveolar macrophages
Azithromycin increases phagocytosis of apoptotic bronchial epithelial cells by alveolar macrophages
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DOI：
10.1183/09031936.06.00001506
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发表时间：
2006-09-01
影响因子：
24.3
通讯作者：
Reynolds, P. N.
中科院分区：
文献类型：
--
作者：
Hodge, S.;Hodge, G.;Reynolds, P. N.
慢性阻塞性肺疾病（COPD）与气道中细胞凋亡增加和吞噬功能缺陷有关。由于未清除的细胞可能发生继发性坏死并使炎症持续存在，因此改善清除的策略将具有治疗意义。有证据表明，15元大环内酯类抗生素阿奇霉素具有抗炎特性。由于其在肺泡巨噬细胞（AM）中达到高浓度的能力，其在肺部的作用可能会增强。本研究探讨了低剂量（500 ng.mL（-1））阿奇霉素对AM吞噬凋亡支气管上皮细胞和中性粒细胞的影响。流式细胞仪测定凋亡细胞的吞噬功能和参与AM识别的受体。用流式细胞仪检测细胞因子，COPD患者的基线吞噬功能较对照组降低。阿奇霉素显著提高了上皮细胞或嗜中性粒细胞的吞噬功能的AM从COPD受试者分别为68%和38%，往往高达与controls.The增加的吞噬功能被部分抑制磷脂酰丝氨酸，牵连的磷脂酰丝氨酸途径在阿奇霉素的促吞噬作用。阿奇霉素对其他识别分子（粒细胞-巨噬细胞集落刺激因子、CD 44、CD 31、CD 36、CD 91、α v β 3整联蛋白）无影响。在较高剂量下，阿奇霉素降低了促炎细胞因子的水平。因此，低剂量阿奇霉素治疗可为慢性阻塞性肺疾病提供一种辅助治疗选择。
Chronic obstructive pulmonary disease (COPD) is associated with increased apoptosis and defective phagocytosis in the airway. As uncleared cells can undergo secondary necrosis and perpetuate inflammation, strategies to improve clearance would have therapeutic significance. There is evidence that the 15-member macrolide antibiotic azithromycin has anti-inflammatory properties. Its effects may be increased in the lung due to its ability to reach high concentrations in alveolar macrophages (AMs).The present study investigated the effects of low-dose (500 ng.mL(-1)) azithromycin on the phagocytosis of apoptotic bronchial epithelial cells and neutrophils by AMs. Flow cytometry was applied to measure phagocytosis and receptors involved in AM recognition of apoptotic cells. Cytokines were investigated using cytometric bead array.Baseline phagocytosis was reduced in COPD subjects compared with controls. Azithromycin significantly improved the phagocytosis of epithelial cells or neutrophils by AMs from COPD subjects by 68 and 38%, respectively, often up to levels comparable with controls.The increase in phagocytosis was partially inhibited by phosphatidylserine, implicating the phosphatidylserine pathway in the pro-phagocytic effects of azithromycin. Azithromycin had no effect on other recognition molecules (granulocyte-macrophage colony-stimulating factor, CD44, CD31, CD36, CD91, alpha v beta 3 integrin). At higher doses, azithromycin decreased levels of proinflammatory cytokines. Thus, low-dose azithromycin therapy could provide an adjunct therapeutic option in chronic obstructive pulmonary disease.