Cellular and molecular mechanisms in chronic obstructive pulmonary disease: An overview

A. Di Stefano, G. Caramori, F. L M Ricciardolo, A. Capelli, I. M. Adcock, C. F. Donner

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

In the last decade, the analysis of bronchial biopsies and lung parenchyma obtained from chronic obstructive pulmonary disease (COPD) patients compared with those from smokers with normal lung function and non-smokers has provided new insights on the role of the different inflammatory and structural cells, their signalling pathways and mediators, contributing to a better knowledge of the pathogenesis of COPD. This review summarizes and discusses the lung pathology of COPD patients with emphasis on inflammatory cell phenotypes that predominate in different clinical conditions. In bronchial biopsies, a cascade of events takes place during progression from mild-to-severe disease. T lymphocytes, particularly CD8+ cells and macrophages are the prevalent inflammatory cells in the lung of healthy smokers and patients with mild COPD, while total and activated neutrophils predominate in severe COPD. The number of CD4+, CD8+ cells and macrophages expressing nuclear factor-kappa B (NF-κB), STAT-4 and IFN-γ proteins as well as endothelial adhesion molecule-1 in endothelium is increased in mild/moderate disease. In contrast, activated neutrophils (MPO+ cells) and increased nitrotyrosine immunoreactivity develops in severe COPD. In bronchial biopsies obtained during COPD exacerbations, some studies have shown an increased T cell and granulocyte infiltration. Regular treatment with high doses of inhaled glucocorticoids does not significantly change the number of inflammatory cells in bronchial biopsies from patients with moderate COPD. The profile in lung parenchyma is similar to bronchial biopsies. 'Healthy' smokers and mild/moderate diseased patients show increased T lymphocyte infiltration in the peripheral airways. Pulmonary emphysema is associated with a general increase of inflammatory cells in the alveolar septa. The molecular mechanisms driving the lymphocyte and neutrophilic prevalence in mild and severe disease, respectively, needs to be extensively studied. Up-regulation of pro-inflammatory transcription factors NF-κB and STAT-4 in mild, activated epithelial and endothelial cells in the more severe disease may contribute to this differential prevalence of infiltrating cells.

Original languageEnglish
Pages (from-to)1156-1167
Number of pages12
JournalClinical and Experimental Allergy
Volume34
Issue number8
DOIs
Publication statusPublished - Aug 2004

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Chronic Obstructive Pulmonary Disease
Biopsy
Lung
NF-kappa B
T-Lymphocytes
Neutrophils
Macrophages
Alveolar Epithelial Cells
Pulmonary Emphysema
Granulocytes
Glucocorticoids
Endothelium
Disease Progression
Transcription Factors
Up-Regulation
Endothelial Cells
Cell Count
Epithelial Cells
Lymphocytes
Pathology

ASJC Scopus subject areas

  • Immunology

Cite this

Cellular and molecular mechanisms in chronic obstructive pulmonary disease : An overview. / Di Stefano, A.; Caramori, G.; Ricciardolo, F. L M; Capelli, A.; Adcock, I. M.; Donner, C. F.

In: Clinical and Experimental Allergy, Vol. 34, No. 8, 08.2004, p. 1156-1167.

Research output: Contribution to journalArticle

Di Stefano, A. ; Caramori, G. ; Ricciardolo, F. L M ; Capelli, A. ; Adcock, I. M. ; Donner, C. F. / Cellular and molecular mechanisms in chronic obstructive pulmonary disease : An overview. In: Clinical and Experimental Allergy. 2004 ; Vol. 34, No. 8. pp. 1156-1167.
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