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

Journal article
Authors M. Erriah
K. Pabreja
M. Fricker
K. J. Baines
L. E. Donnelly
Johan Bylund
Anna Karlsson
J. L. Simpson
Journal Of Biological Chemistry V. P. Rlsson Sr
Published in Respiratory Research
Volume 20
ISSN 1465-993X
Publication year 2019
Published at Institute of Odontology
Institute of Medicine, Department of Rheumatology and Inflammation Research
Language en
Links dx.doi.org/10.1186/s12931-018-0967-...
Keywords Asthma, Galectin-3, Macrophage, Neutrophil, Efferocytosis, Inflammation, expression, phagocytosis, clearance, kinase, cells, Respiratory System
Subject categories Clinical Medicine

Abstract

BackgroundGalectin-3 is a 32kDa 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.MethodsEligible 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 (50g/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.ResultsBaseline 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.Conclusions p id=Par4 Galectin-3 modulates macrophage function in asthma, indicating a potential role for galectin-3 to reverse impaired efferocytosis in NEA.

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