The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Alveolar macrophages from subjects with chronic obstructive pulmonary disease are deficient in their ability to phagocytose apoptotic airway epithelial cells
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Impaired phagocytosis and clearance of cellular debris by airway macrophages in COPD result in persistent inflammation (85, 104).”
From Aging and Lung Disease (2020) · cites this paper as [104]
In the citing paper
“Specifically, macrophages, which can produce multiple proinflammatory cytokines and secrete MMPs, are the most abundant cell type in the BAL fluid of COPD patients, and increased numbers correlate with disease severity (85, 86, 104).”
From Aging and Lung Disease (2020) · cites this paper as [104]
In the citing paper
“Due to reduced immunity, coexisting comorbidities, and age-associated functional limitations, the incidence of severe sepsis and septic shock increases in older individuals (104, 146).”
From Aging and Lung Disease (2020) · cites this paper as [104]
Citations
Cites
Disruption of epithelial cell-matrix interactions induces apoptosis
Frisch, S., & Francis, H. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.124.4.619 · Cited by 3,276
Inhibition of VEGF receptors causes lung cell apoptosis and emphysema
Kasahara, Y., Tuder, R. M., Taraseviciene‐Stewart, L., Cras, T. D. L., Abman, S. H., Hirth, P., Waltenberger, J. L., & Voelkel, N. F. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10259 · Cited by 1,113
Savill, J., Hogg, N., Ren, Y., & Haslett, C. (1992) · Journal of Clinical Investigation · doi:10.1172/jci116019 · Cited by 818
Flow cytometry of apoptotic cell death
Vermes, I., Haanen, C., & Reutelingsperger, C. P. M. (2000) · Journal of Immunological Methods · doi:10.1016/s0022-1759(00)00233-7 · Cited by 808
Pauwels, R., Buist, A. S., Calverley, P., Jenkins, C. R., Hurd, S. S., & Lenfant, C. J. M. (2001) · Respiratory Care · doi:10.1177/002013240104600806 · Cited by 614
Segura-Valdéz, M. D. L., Pardo, A., Gaxiola, M., Uhal, B. D., Becerril, C., & Selman, M. (2000) · CHEST Journal · doi:10.1378/chest.117.3.684 · Cited by 507
Trautmann, A., Akdiş, M., Kleemann, D., Altznauer, F., Simon, H., Graeve, T., Noll, M., Bröcker, E., Blaser, K., & Akdiş, C. A. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9199 · Cited by 495
Fadok, V. A., Warner, M. L., Bratton, D. L., & Henson, P. M. (1998) · PubMed · Cited by 406
Vandivier, R. W., Fadok, V. A., Hoffmann, P. R., Bratton, D. L., Penvari, C., Brown, K. K., Brain, J. D., Accurso, F. J., & Henson, P. M. (2002) · Journal of Clinical Investigation · doi:10.1172/jci13572 · Cited by 373
Fadok, V. A., Warner, M. L., Bratton, D. L., & Henson, P. M. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.11.6250 · Cited by 353
Research works printed but not linked: 1
- Gibson P, 1997, Pulmonary macrophage phagocytosis of apoptotic neutrophils is mediated by thrombospondin and its receptors‐avb3 and CD36, Am. J. Respir. Crit. Care Med., 155, A296
Cited by
Sorted by citations
Items 401–439 of 439
Trauma, Regulated Cell Death, and Inflammation
Fan, J., & Fan, L. (2016) · Springer eBooks · doi:10.1007/978-981-10-2425-2_16
Fedosenko, S. V., Chernogoryuk, G. E., Кириллова, Н. А., Фисенко, А. Ю., & Roslyakova, Y. P. (2011) · Bulletin of Siberian Medicine · doi:10.20538/1682-0363-2011-6-52-56
Barnawi, J. (2016) · Adelaide Research & Scholarship (AR&S) (University of Adelaide) · doi:10.4225/55/5824141d2fa45
Nitric oxide as the main multifunctional regulator of immunocompetent and endothelial cells
Sadlyak, O. V., Kolishetska, М. А., Baida, M. L., Мусій-Семенців, Х. Г., Sementsiv, N. G., & Lesyk, R. (2017) · Biopolymers and Cell · doi:10.7124/bc.000957
Cruz, T. (2017) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Khorasani, N. M. (2015) · Spiral (Imperial College London) · doi:10.25560/52433
Moreira, A. R. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.5.2019.tde-15012019-091300
Yeo, S. C. M. (2016) · Spiral (Imperial College London) · doi:10.25560/69790
Macrophage plasticity in chronic obstructive pulmonary disease
Day, A. (2016) · Spiral (Imperial College London) · doi:10.25560/68514
Jenkins, A. R. (2019) · Lincoln Repository (University of Lincoln) · doi:10.24385/lincoln.24326113
Fedosenko, S. V., Черногорюк, Г. Э., & Рослякова, Е. П. (2010) · PULMONOLOGIYA · doi:10.18093/0869-0189-2010-5-56-60
Efficiency of immune-regulating therapy in patients with chronic obstructive pulmonary disease
Farchutdinov, U. R., & Farchutdinov, S. U. (2008) · PULMONOLOGIYA · doi:10.18093/0869-0189-2008-0-5-66-70
THE BANALITY OF IMMUNITY, DEATH AND DISTRESS OF TOBACCO SMOKING --("STRIKE THE RIGHT”)
Rao, M. V. R., Kumari, A., Calvo, T., Khan, A. A., Mathai, D. C., Rao, D. S., Priscilla, T., Verma, M. K., & Chennamchetty, V. K. (2021) · GLOBAL JOURNAL FOR RESEARCH ANALYSIS · doi:10.36106/gjra/3912068
Салухов, В. В., Анатольевич, Х. М., Pivovich, A. V., & Игоревич, В. Н. (2021) · Bulletin of the Russian Military Medical Academy · doi:10.17816/brmma63652
Bacterial Colonization in COPD
Donnelly, L. (2021) · Elsevier eBooks · doi:10.1016/b978-0-08-102723-3.00242-0
The roles of macrophages in mediating the homeostatic process
Mitra, A., & Cho, J. Y. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-822368-0.00018-9
Macrophages in respiratory system
Uddin, M. B., Sajib, E. H., Hoque, S. F., Hassan, M. M., & Ahmed, S. S. U. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-822368-0.00014-1
Sapey, E. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.726785757.793558944
Inflammasomes in cigarette smoke- or ozone-induced lung diseases
Riteau, N., Huot-Marchand, S., & Couillin, I. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-91802-2.00015-3 · Cited by 1
The effect of obstructive lung diseases and smoking on macrophages
van der Veen, A. (2023) · University of Groningen research database (University of Groningen / Centre for Information Technology) · doi:10.33612/diss.360054616
Raju, D., Munta, A. K., & Lalitha, D. L. (2021) · International Journal of Health Sciences · doi:10.53730/ijhs.v6ns9.14067
“Smoking impairs degradation of apoptotic neutrophils and TNF-α impairs the uptake of apoptotic cells by macrophages which leads to secondary necrosis in apoptotic cells releasing proinflammatory substances [19, 20].”
Wang, J., Kanmani, P., & Hu, G. (2024) · The Journal of Immunology · doi:10.1093/jimmun/vkag109
Siglec-F Protects Against Elastase-induced Lung Inflammation and Emphysema in MicePreprint
Ye, Q., Hara, N., Hu, Y., Orlov, M., Smith, B. J., Brunetti, T. M., Blumhagen, R. Z., Liu, Z., Gao, B., Königshoff, M., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.16.674299
Singh, R., Belchamber, K. B. R., Fenwick, P. S., Chana, K. K., Donaldson, G. C., Wedzicha, J. A., Barnes, P. J., & Donnelly, L. E. (2021) · Figshare · doi:10.6084/m9.figshare.14456861
Singh, R., Belchamber, K. B. R., Fenwick, P. S., Chana, K. K., Donaldson, G. C., Wedzicha, J. A., Barnes, P. J., & Donnelly, L. E. (2021) · Figshare · doi:10.6084/m9.figshare.14456864
Tran, H. B., Hamon, R., Jersmann, H. P. A., Ween, M. P., Asare, P. F., Haberberger, R. V., Pant, H., & Hodge, S. J. (2021) · Figshare · doi:10.6084/m9.figshare.14650656
Self-citationORMDL3 and Sphingolipid Metabolism in Human Airway Inflammatory Diseases
Chi, S., & Zhang, Y. (2025) · Springer eBooks · doi:10.1007/978-3-031-55254-0_20-1
Redwan, B., Biancosino, C., Fischer, S., Janciauskiene, S. M., & Golpon, H. A. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27104627
“…markedly reduced uptake of apoptotic airway epithelial cells compared with healthy controls (~12% vs. ~26%), whereas general phagocytosis of inert particles remains intact—indicating a specific defect at the level of efferocytic receptor signaling rather than a global phagocytic impairment [2].”
Redwan, B., Biancosino, C., Mehdizadeh‐Shrifi, A., Lennartz, F. N., Fischer, S., Wiebe, K., Schael, M., Zardo, P., Janciauskiene, S. M., & Golpon, H. A. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27157045
“The observation that viable, but not apoptotic, lymphocytes markedly increased epithelial VEGF secretion further suggests that the cellular microenvironment, including the dying cells and their impaired clearance in COPD, may contribute to the regulation of angiogenic signaling [10–12].”
InfluentialEpigenetic regulation of alveolar macrophage homeostasis by histone deacetylase 1 and 2
Lai, W., Luo, M., Wang, Y., Wang, Y., Li, X., He, Z., Cui, Q., Wu, T., & Wu, L. (2026) · Immunity & Inflammation · doi:10.1007/s44466-026-00057-x · Cited by 1
“PAP is a prototypic disorder caused by defective AM maturation and surfactant clearance [47, 48], whereas reduced HDAC2 expression and activity have been reported in AMs from patients with COPD and correlate with disease severity [32, 49, 50].”
Alteracions vasculars pulmonars induïdes per l’exposició a fum de tabac en un model animal de MPOC
Andrés, E. F. (2011) · Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona)
Magnani, K. L. (2009) · Americanae (AECID Library)
Air Pollution and Chronic Obstructive Airway Disease
Redai, I. G., & Haczku, A. (2015) · Molecular and integrative toxicology · doi:10.1007/978-1-4471-6669-6_5
Metadata
- Authors
- Hodge, S., Hodge, G., Scicchitano, R., Reynolds, P. N., & Holmes, M.
- Affiliations
- Royal Adelaide Hospital (AU)
- Women's and Children's Hospital (AU)
- 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
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
