Cited by 440Chronic Obstructive Pulmonary Disease (COPD) ResearchPhagocytosis and Immune RegulationOccupational and environmental lung diseases

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Alveolar macrophages from subjects with chronic obstructive pulmonary disease are deficient in their ability to phagocytose apoptotic airway epithelial cells

Hodge, Sandra, Hodge, Greg, Scicchitano, Raffaele, Reynolds, Paul N, Holmes, Mark·2003·Immunology & Cell Biology

DOI 10.1046/j.1440-1711.2003.t01-1-01170.x

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Abstract

Chronic obstructive pulmonary disease is a highly prevalent, complex disease, usually caused by cigarette smoke. It causes serious morbidity and mortality and costs the global community billions of dollars per year. While chronic inflammation, extracellular matrix destruction and increased airway epithelial cell apoptosis are reported in chronic obstructive pulmonary disease, the understanding of the basic pathogenesis of the disease is limited and there are no effective treatments. We hypothesized that the accumulation of apoptotic airway epithelial cells chronic obstructive pulmonary disease in could be due to defective phagocytic clearance by alveolar macrophages. There have been no previous studies of the phagocytic capacity of alveolar macrophages in chronic obstructive pulmonary disease using physiologically relevant apoptotic airway epithelial cells as phagocytic targets. We developed a phagocytosis assay whereby cultured 16HBE airway epithelial cells were induced to apoptosis with ultraviolet radiation and stained with mitotracker green. Alveolar macrophages from bronchoalveolar lavage from eight control and six chronic obstructive pulmonary disease subjects were analysed following 1.5 h incubation with apoptotic airway epithelial cells, then staining with macrophage marker anti CD33. CD33+/mitotracker green + events (i.e., alveolar macrophages which had phagocytosed apoptotic airway epithelial cells) were analysed using flow cytometry. Phagocytosis of polystyrene microbeads was investigated in parallel. A significantly reduced proportion of alveolar macrophages from chronic obstructive pulmonary disease subjects ingested apoptotic airway epithelial cells compared with controls (11.6 ± 4.1% for chronic obstructive pulmonary disease versus 25.6 ± 9.2% for control group). Importantly, the deficiency was not observed using polystyrene beads, suggesting that the failure to resolve epithelial damage in chronic obstructive pulmonary disease may result, at least partially, from specific defects in phagocytic ability of alveolar macrophages to ingest apoptotic airway epithelial cells.

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Background
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“Hodge and colleagues identified an abnormal accumulation of epithelial cells undergoing apoptosis in the airways of adults with chronic inflammatory lung diseases including COPD and asthma [154,155].”
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Authors: Hodge, S., Hodge, G., Scicchitano, R., Reynolds, P. N., & Holmes, M.
Affiliations: Royal Adelaide Hospital (AU)
Women's and Children's Hospital (AU)
ORCID: Hodge, Sandra
Hodge, Greg
Reynolds, Paul N
Holmes, Mark
Venue: Immunology & Cell Biology
Publisher: Wiley
Published: 2003-08
Volume: 81
Issue: 4
Pages: 289-296
ISSN: 0004-945X (ISSN-L)
0818-9641
1440-1711
DOI: 10.1046/j.1440-1711.2003.t01-1-01170.x
OpenAlex: W1980191732
Cited by: 440
References: 32
Citations by year: 2026: 7 · 2025: 15 · 2024: 17 · 2023: 12 · 2022: 17 · 2021: 34 · 2020: 19 · 2019: 17 · 2018: 23 · 2017: 21 · 2016: 28 · 2015: 28 · 2014: 13 · 2013: 32 · 2012: 20
FWCI: 11.12
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Immunology and Cell Biology (publishedVersion)
PubMed (publishedVersion)
Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
Funders: Royal Adelaide Hospital
Australian Lung Foundation
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
Keywords: chronic obstructive pulmonary disease, alveolar macrophages, phagocytosis, cigarette smoke, 16HBE cells, MitoTracker Green, CD33, phagocytic defects
MeSH terms: Aged, Antibodies, Monoclonal, Bronchoalveolar Lavage Fluid, Cell Line, Transformed, Cell Survival, Epithelial Cells, Flow Cytometry, Humans, Phagocytosis, Macrophages, Alveolar, Apoptosis, Respiratory Mucosa, Pulmonary Disease, Chronic Obstructive

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Alveolar macrophages from subjects with chronic obstructive pulmonary disease are deficient in their ability to phagocytose apoptotic airway epithelial cells

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