An Immune Basis for Lung Parenchymal Destruction in Chronic Obstructive Pulmonary Disease and Emphysema
Open accessAbstract
BACKGROUND: Chronic obstructive pulmonary disease and emphysema are a frequent result of long-term smoking, but the exact mechanisms, specifically which types of cells are associated with the lung destruction, are unclear. METHODS AND FINDINGS: We studied different subsets of lymphocytes taken from portions of human lungs removed surgically to find out which lymphocytes were the most frequent, which cell-surface markers these lymphocytes expressed, and whether the lymphocytes secreted any specific factors that could be associated with disease. We found that loss of lung function in patients with chronic obstructive pulmonary disease and emphysema was associated with a high percentage of CD4+ and CD8+ T lymphocytes that expressed chemokine receptors CCR5 and CXCR3 (both markers of T helper 1 cells), but not CCR3 or CCR4 (markers of T helper 2 cells). Lung lymphocytes in patients with chronic obstructive pulmonary disease and emphysema secrete more interferon gamma--often associated with T helper 1 cells--and interferon-inducible protein 10 and monokine induced by interferon, both of which bind to CXCR3 and are involved in attracting T helper 1 cells. In response to interferon-inducible protein 10 and monokine induced by interferon, but not interferon gamma, lung macrophages secreted macrophage metalloelastase (matrix metalloproteinase-12), a potent elastin-degrading enzyme that causes tissue destruction and which has been linked to emphysema. CONCLUSIONS: These data suggest that Th1 lymphoctytes in the lungs of people with smoking-related damage drive progression of emphysema through CXCR3 ligands, interferon-inducible protein 10, and monokine induced by interferon.
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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.
“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 [85]
Impaired phagocytosis and clearance of cellular debris by airway macrophages in COPD result in persistent inflammation.
“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 [85]
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Self-citation
- Authors
- Grumelli, S., Corry, D. B., Song, L.-Z., Song, L., Green, L., Huh, J., Hacken, J., Espada, R., Bag, R., Lewis, D. E., & Kheradmand, F.
- Affiliations
- Baylor College of Medicine (US)
- Michael E. DeBakey VA Medical Center (US)
- Corresponding author
- Kheradmand, Farrah
- Venue
- PLoS Medicine
- Publisher
- Public Library of Science (PLoS)
- Published
- 2004-10-19
- Volume
- 1
- Issue
- 1
- Pages
- e8
- ISSN
- 1549-1277 (ISSN-L)
- 1549-1676
- PMC
- PMC523885
- OpenAlex
- W2108679807
- Cited by
- 484
- References
- 59
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 21 · 2023: 12 · 2022: 11 · 2021: 21 · 2020: 14 · 2019: 22 · 2018: 16 · 2017: 25 · 2016: 21 · 2015: 28 · 2014: 15 · 2013: 29 · 2012: 31
- FWCI
- 19.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Public Health Service (69585, 64061, 72419)
- National Institute of Allergy and Infectious Diseases (P30AI036211, AI 36211)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- chronic obstructive pulmonary disease, emphysema, Th1 cells, CXCR3, CCR5, interferon-gamma, CXCL10, macrophage metalloelastase, matrix metalloproteinase-12, elastin degradation, smoking, lung lymphocytes, chemokine receptors
- MeSH terms
- Aged, Female, Humans, Male, Middle Aged, Pulmonary Emphysema, Smoking, Tomography, X-Ray Computed, Lymphocyte Subsets, Cytokines, Macrophages, Alveolar, Th1 Cells, Disease Progression, Receptors, Chemokine, Chemokines, CXC, Pulmonary Disease, Chronic Obstructive, Chemokine CXCL10, Receptors, CXCR3
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