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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

Galectin-3 modulates macrophage function in asthma, indicating a potential role for galectin-3 to reverse impaired efferocytosis in NEA.

• Authors: Melanie Erriah, Kavita Pabreja, Michael Fricker, Katherine J Baines, Louise E Donnelly, Johan Bylund, Anna Karlsson, Jodie L Simpson
• Journal: Respiratory research (Respir Res) Vol. 20 Issue 1 Pg. 1 (Jan 03 2019) ISSN: 1465-993X [Electronic] England
• PMID: 30606211 (Publication Type: Journal Article)

Chemical References

• Blood Proteins
• Galectin 3
• Galectins
• LGALS3 protein, human

Topics

• Adult
• Aged
• Apoptosis (drug effects, physiology)
• Asthma (metabolism)
• Blood Proteins
• Cells, Cultured
• Female
• Galectin 3 (biosynthesis, pharmacology)
• Galectins
• Granulocytes (drug effects, metabolism)
• Humans
• Macrophages (metabolism)
• Male
• Middle Aged
• Phagocytosis (drug effects, physiology)