BACKGROUND Alveolar macrophages are professional phagocytes that remove microbial pathogens inhaled into the lung. The phagocytic ability is compromised in chronic obstructive pulmonary disease (COPD). However, the molecular mechanisms underlying this defect in phagocytosis are not clearly defined. MATERIALS AND METHODS Cell suspensions were collected from lung tissues of patients undergoing lung resection. Alveolar macrophages were detected as FSChi/ SSChi/CD45+/CD206+ cells in the isolated cell suspension by flow-cytometry. The cell surface expression of plasma membrane-bound phagocytic receptors (Fcγ receptor I (FcγRI), a complement receptor CD11b, macrophage scavenger receptor-1 (MSR-1), CD36 and Siglec-1) was determined on the alveolar macrophages. Correlations between the expression levels of the phagocytic receptors and disease severity were analysed. Phagocytosis of fluorescence-tagged bacteria by human alveolar macrophages was evaluated. RESULTS The flow-cytometry analyses revealed that FcγRI, CD11b, MSR-1 and Siglec-1, but not CD36, were expressed on human alveolar macrophages. Among these receptors, Siglec-1 expression was significantly decreased on alveolar macrophages in COPD ex-smokers (n = 11), compared to control never-smokers (n = 11) or control ex-smokers (n = 9). The Siglec-1 expression on alveolar macrophages was significantly correlated with lung function (forced expiratory volume in 1 s) and with the severity of emphysema. Treatment of human alveolar macrophages with an anti-Siglec1 blocking antibody decreased phagocytosis of non-typeable Haemophilus influenzae (NTHi). CONCLUSION Our findings demonstrated reduced expression of Siglec-1 on alveolar macrophages in COPD, which is involved in engulfment of NTHi.

中文翻译：

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在慢性阻塞性肺疾病中，吞噬受体Siglec-1在肺泡巨噬细胞上的表达降低。

背景技术肺泡巨噬细胞是专业吞噬细胞，其去除吸入肺中的微生物病原体。在慢性阻塞性肺疾病（COPD）中，吞噬能力受到损害。但是，吞噬作用的这一缺陷的分子机制尚不清楚。材料与方法从接受肺切除的患者的肺组织中收集细胞悬液。通过流式细胞术在分离的细胞悬液中将肺泡巨噬细胞检测为FSChi / SSChi / CD45 + / CD206 +细胞。测定在肺泡巨噬细胞上质膜结合的吞噬受体（Fcγ受体I（FcγRI），补体受体CD11b，巨噬细胞清道夫受体-1（MSR-1），CD36和Siglec-1）在细胞表面的表达。分析了吞噬受体表达水平与疾病严重程度之间的相关性。评估了人类肺泡巨噬细胞对荧光标记细菌的吞噬作用。结果流式细胞仪分析显示在人肺泡巨噬细胞上表达了FcγRI，CD11b，MSR-1和Siglec-1，但没有表达CD36。在这些受体中，与从未吸烟者（n = 11）或正常人（n = 9）相比，COPD吸烟者（n = 11）的肺泡巨噬细胞上的Siglec-1表达显着降低。肺泡巨噬细胞上的Siglec-1表达与肺功能（强迫呼气量1 s）和肺气肿的严重程度显着相关。用抗Siglec1阻断抗体治疗人肺泡巨噬细胞可减少不可分型流感嗜血杆菌（NTHi）的吞噬作用。