Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryocho, Aobaku, Sendai, 980 8574, Japan.
Department of Thoracic Surgery, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, 986 8522, Japan.
Respir Res. 2020 Jan 28;21(1):30. doi: 10.1186/s12931-020-1297-2.
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.
Cell suspensions were collected from lung tissues of patients undergoing lung resection. Alveolar macrophages were detected as FSC/ SSC/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.
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).
Our findings demonstrated reduced expression of Siglec-1 on alveolar macrophages in COPD, which is involved in engulfment of NTHi.
肺泡巨噬细胞是一种专业的吞噬细胞，可清除吸入肺部的微生物病原体。在慢性阻塞性肺疾病（COPD）中，吞噬能力受损。然而，吞噬作用缺陷的分子机制尚不清楚。
从接受肺切除术的患者的肺组织中收集细胞悬浮液。通过流式细胞术，在分离的细胞悬浮液中，肺泡巨噬细胞被鉴定为 FSC/SSC/CD45/CD206 细胞。在肺泡巨噬细胞上测定细胞膜结合吞噬受体（FcγRI（FcγRI）、补体受体 CD11b、巨噬细胞清道夫受体-1（MSR-1）、CD36 和 Siglec-1）的表面表达。分析吞噬受体表达水平与疾病严重程度之间的相关性。评估人肺泡巨噬细胞吞噬荧光标记细菌的能力。
流式细胞术分析显示，FcγRI、CD11b、MSR-1 和 Siglec-1，但不是 CD36，在人肺泡巨噬细胞上表达。在这些受体中，COPD 戒烟者（n=11）肺泡巨噬细胞上的 Siglec-1 表达明显低于对照组从不吸烟者（n=11）或对照组戒烟者（n=9）。肺泡巨噬细胞上 Siglec-1 的表达与肺功能（1 秒用力呼气量）和肺气肿严重程度显著相关。用抗 Siglec1 阻断抗体处理人肺泡巨噬细胞可降低非典型流感嗜血杆菌（NTHi）的吞噬作用。
我们的研究结果表明，COPD 患者肺泡巨噬细胞上 Siglec-1 的表达减少，这与 NTHi 的吞噬作用有关。
