What's the deal with efferocytosis and asthma?
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ABSTRACT:
SUBMITTER: Martinez J
PROVIDER: S-EPMC9843639 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
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What's the deal with efferocytosis and asthma?
Martinez Jennifer J Cook Donald N DN
Trends in immunology 20210906 10
Mucosal sites, such as the lung, serve as crucial, yet vulnerable barriers to environmental insults such as pathogens, allergens, and toxins. Often, these exposures induce massive infiltration and death of short-lived immune cells in the lung, and efficient clearance of these cells is important for preventing hyperinflammation and resolving immunopathology. Herein, we review recent advances in our understanding of efferocytosis, a process whereby phagocytes clear dead cells in a noninflammatory ...[more]
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Project description:The Global Initiative for Asthma (GINA) was established in 1993 by the World Health Organization and National Heart Lung and Blood Institute to develop a global strategy for managing and preventing asthma. GINA reports, now funded independently through the sale of GINA products, have provided the foundation for many national guidelines. They are prepared by international experts from primary, secondary and tertiary care, and are annually updated following a review of evidence. In 2014, a major revision of the GINA report was published, that took into account advances in evidence not only about asthma and its treatment, but also about how to improve implementation of evidence-based recommendations in clinical practice. This paper summarises key changes relevant to primary care in the new GINA report. A noticeable difference is the report's radically different approach, now clinically-focussed, with multiple practical tools and flow charts to improve its utility for busy frontline clinicians. Key changes in recommendations include a new, diagnosis-centred definition of asthma; more detail about how to assess current symptom control and future risk; a comprehensive approach to tailoring treatment for individual patients; expanded indications for commencing inhaled corticosteroids; new recommendations for written asthma action plans; a new chapter on diagnosis and initial treatment of patients with asthma-COPD overlap syndrome; and a revised approach to diagnosing asthma in preschool children. The 2014 GINA report (further updated in 2015) moved away from a 'textbook' approach to provide clinicians with up-to-date evidence about strategies to control symptoms and minimise asthma risk, in a practical, practice-centred format.
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Project description:BackgroundGalectin-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.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 (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.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.ConclusionsGalectin-3 modulates macrophage function in asthma, indicating a potential role for galectin-3 to reverse impaired efferocytosis in NEA.
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