Galectin-3 enhances monocyte-derived macrophage efferocytosis of apoptotic granulocytes in asthma

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 (COP...

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Published in:	Respiratory research 2019-01, Vol.20 (1), p.1-1, Article 1
Main Authors:	Erriah, Melanie, Pabreja, Kavita, Fricker, Michael, Baines, Katherine J, Donnelly, Louise E, Bylund, Johan, Karlsson, Anna, Simpson, Jodie L
Format:	Article
Language:	eng
Subjects:	Adult Adults Aged Airway management Apoptosis Apoptosis - drug effects Apoptosis - physiology Asthma Asthma - metabolism Binding proteins Care and treatment Cell activation Cell culture cells Cells, Cultured Chemotaxis Chronic obstructive pulmonary disease clearance Clinical Medicine Development and progression Efferocytosis Enzyme-linked immunosorbent assay Ethics expression Female Flow cytometry Fluorescence Fluorescence microscopy Galectin 3 - biosynthesis Galectin 3 - pharmacology Galectin-3 Granulocytes Granulocytes - drug effects Granulocytes - metabolism Health aspects Humans Immunofluorescence Inflammation Interleukin Interleukin 6 kinase Klinisk medicin Leukocytes (eosinophilic) Leukocytes (granulocytic) Lung diseases Macrophage Macrophages Macrophages - metabolism Male Middle Aged Monocytes Neutrophil Neutrophils Obesity Obstructive lung disease Phagocytosis Phagocytosis - drug effects Phagocytosis - physiology Physiological aspects Proteins Respiratory System Respiratory tract Smoking Sputum
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Summary:	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.
ISSN:	1465-993X 1465-9921 1465-993X