Decreased expression of a phagocytic receptor Siglec-1 on alveolar macrophages in chronic obstructive pulmonary disease
慢性阻塞性肺疾病肺泡巨噬细胞吞噬受体 Siglec-1 表达降低
- 作者列表："Atsushi Tanno","Naoya Fujino","Mitsuhiro Yamada","Hisatoshi Sugiura","Taizou Hirano","Rie Tanaka","Hirohito Sano","Satoshi Suzuki","Yoshinori Okada","Masakazu Ichinose
Abstract 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.
文摘背景肺泡巨噬细胞是清除吸入肺内微生物病原体的专业吞噬细胞。慢性阻塞性肺疾病 (COPD) 的吞噬能力受损。然而，吞噬功能缺陷的分子机制尚未明确。材料与方法收集行肺切除术患者肺组织细胞悬液。流式细胞术检测肺泡巨噬细胞为 FSChi/sshi/CD45 +/CD206 + 细胞。细胞表面表达质膜结合吞噬受体 (fc γ 受体 I (fc γ ri) 、补体受体 CD11b 、巨噬细胞清道夫受体-1 (MSR-1) 、 CD36 和 Siglec-1) 测定肺泡巨噬细胞。分析吞噬受体表达水平与疾病严重程度的相关性。评价人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，人肺泡巨噬细胞表面有 fc γ ri 、 CD11b 、 MSR-1 和 Siglec-1，但无 CD36 表达。在这些受体中，与不吸烟者 (n = 11) 相比，吸烟 COPD 患者肺泡巨噬细胞上的 Siglec-1 表达显著降低 (n = 11)。或控制戒烟者 (n = 9)。肺泡巨噬细胞上的 Siglec-1 表达与肺功能 (1 s 用力呼气容积) 和肺气肿严重程度显著相关。用 anti-Siglec1 阻断抗体治疗人肺泡巨噬细胞可降低不可分型流感嗜血杆菌 (NTHi) 的吞噬功能。结论 COPD 肺泡巨噬细胞 Siglec-1 表达减少，参与 NTHi 的吞噬。
METHODS::Translation of genomic alterations to protein changes in chronic obstructive pulmonary disease (COPD) is largely unexplored. Using integrated proteomic and RNA sequencing analysis of COPD and control lung tissues, we identified a protein signature in COPD characterised by extracellular matrix changes and a potential regulatory role for SUMO2. Furthermore, we identified 61 differentially expressed novel, non-reference, peptides in COPD compared with control lungs. This included two peptides encoding for a new splice variant of SORBS1, of which the transcript usage was higher in COPD compared with control lungs. These explorative findings and integrative proteogenomic approach open new avenues to further unravel the pathology of COPD.