Priority Research Centre for Healthy Lungs, The University of Newcastle, Newcastle, NSW, Australia.
Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
Respir Res. 2019 Jan 3;20(1):1. doi: 10.1186/s12931-018-0967-9.
Galectin-3 is a 32 kDa protein secreted by macrophages involved in processes such as cell activation, chemotaxis and phagocytosis. Galectin-3 has previously been shown to improve the ability of airway macrophages to ingest apoptotic cells (efferocytosis) in chronic obstructive pulmonary disease (COPD) and may be of interest in non-eosinophilic asthma (NEA) which is also characterised by impaired efferocytosis. It was hypothesised that the addition of exogenous galectin-3 to monocyte-derived macrophages (MDMs) derived from donors with NEA would enhance their ability to engulf apoptotic granulocytes.
Eligible non-smoking adults with asthma (n = 19), including 7 with NEA and healthy controls (n = 10) underwent a clinical assessment, venepuncture and sputum induction. MDMs were co-cultured with apoptotic granulocytes isolated from healthy donors with or without exogenous recombinant galectin-3 (50 μg/mL) and efferocytosis was assessed by flow cytometry. Galectin-3 expression and localisation in MDMs was visualised by immunofluorescence staining and fluorescence microscopy. Galectin-3, interleukin (IL)-6 and CXCL8 secretion were measured in cell culture supernatants by ELISA and cytometric bead array.
Baseline efferocytosis (mean (±standard deviation)) was lower in participants with asthma (33.2 (±17.7)%) compared with healthy controls (45.3 (±15.9)%; p = 0.081). Efferocytosis did not differ between the participants with eosinophilic asthma (EA) (31.4 (±19.2)%) and NEA (28.7 (±21.5)%; p = 0.748). Addition of galectin-3 significantly improved efferocytosis in asthma, particularly in NEA (37.8 (±18.1)%) compared with baseline (30.4 (±19.7)%; p = 0.012). Efferocytosis was not associated with any of the clinical outcomes but was negatively correlated with sputum macrophage numbers (Spearman r = - 0.671; p = 0.017). Galectin-3 was diffusely distributed in most MDMs but formed punctate structures in 5% of MDMs. MDM galectin-3 secretion was lower in asthma (9.99 (2.67, 15.48) ng/mL) compared with the healthy controls (20.72 (11.28, 27.89) ng/mL; p = 0.044) while IL-6 and CXCL8 levels were similar.
Galectin-3 modulates macrophage function in asthma, indicating a potential role for galectin-3 to reverse impaired efferocytosis in NEA.
半乳糖凝集素-3 是一种 32kDa 的蛋白，由巨噬细胞分泌，参与细胞激活、趋化和吞噬等过程。先前的研究表明，半乳糖凝集素-3 能够提高气道巨噬细胞吞噬凋亡细胞（吞噬作用）的能力，在慢性阻塞性肺疾病（COPD）中，半乳糖凝集素-3 可能具有重要意义，因为它可以改善吞噬作用。非嗜酸性粒细胞性哮喘（NEA）也具有吞噬作用受损的特征，因此也可能对半乳糖凝集素-3 感兴趣。本研究假设向来源于 NEA 患者的单核细胞衍生的巨噬细胞（MDM）中添加外源性半乳糖凝集素-3，能够增强其吞噬凋亡粒细胞的能力。
纳入了 19 名符合条件的非吸烟哮喘患者（包括 7 名 NEA 患者）和 10 名健康对照者，进行临床评估、静脉穿刺和痰诱导。将 MDM 与来自健康供体的凋亡粒细胞共培养，有无外源性重组半乳糖凝集素-3（50μg/mL），通过流式细胞术评估吞噬作用。通过免疫荧光染色和荧光显微镜观察 MDM 中半乳糖凝集素-3 的表达和定位。通过酶联免疫吸附试验（ELISA）和流式细胞术检测细胞培养上清液中的半乳糖凝集素-3、白细胞介素（IL）-6 和 CXCL8 的分泌情况。
与健康对照组（45.3（±15.9）%）相比，哮喘患者的基础吞噬作用（平均值（±标准差））较低（33.2（±17.7）%；p=0.081）。嗜酸性粒细胞性哮喘（EA）（31.4（±19.2）%）和 NEA（28.7（±21.5）%）患者之间的吞噬作用无差异（p=0.748）。添加半乳糖凝集素-3可显著提高哮喘患者的吞噬作用，尤其是 NEA（37.8（±18.1）%），与基础水平（30.4（±19.7）%）相比，差异有统计学意义（p=0.012）。吞噬作用与任何临床结局均无关，但与痰中巨噬细胞数量呈负相关（Spearman r=-0.671；p=0.017）。半乳糖凝集素-3在大多数 MDM 中呈弥散分布，但在 5%的 MDM 中形成点状结构。与健康对照组（9.99（2.67，15.48）ng/mL）相比，哮喘患者的 MDM 半乳糖凝集素-3 分泌量较低（8.24（2.52，15.26）ng/mL；p=0.044），而 IL-6 和 CXCL8 水平相似。
半乳糖凝集素-3 调节哮喘患者的巨噬细胞功能，表明半乳糖凝集素-3 可能通过逆转 NEA 中受损的吞噬作用发挥作用。
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