Alveolar inflammation and its relation to emphysema in smokers.

Finkelstein, Richard A.; Fraser, Robert S.; Ghezzo, Heberto; Cosio, Manuel G.

doi:10.1164/ajrccm.152.5.7582312

Cited by 395 publications

(305 citation statements)

References 26 publications

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“…The demonstration of an inverse relationship between the number of infiltrating neutrophils and pack years is consistent with another previous study which has noted a similar reduction in the number of neutrophils infiltrating the alveolar septum associated with cigarette smoking [23]. However, the data are in contrast to the authors' previous findings [15] and those of BOSKEN et al [24] in which amount smoked correlated positively with the number of infiltrating neutrophils in the small airways.…”

Section: Discussionsupporting

confidence: 90%

Subepithelial immunopathology of the large airways in smokers with and without chronic obstructive pulmonary disease

2000

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Previous work has shown an increase in CD8+ T-cells, neutrophils and eosinophils in small airway subepithelium in smokers. The authors have now investigated whether similar changes occur in the large airways.Immunohistochemistry on frozen sections of bronchial biopsies were obtained at bronchoscopy in 11 nonsmokers, eight asymptomatic smokers and 11 smokers with chronic bronchitis and chronic obstructive pulmonary disease (COPD).There was an increase in the number of CD8+ cells infiltrating the bronchial subepithelium in the COPD group compared to the asymptomatic smokers (305 (109± 400) versus 92 (41±550) cells . mm -2 , p=0.030). There was a negative correlation between the number of CD8+ cells and the forced expiratory volume in one second (FEV1) %predicted (p=0.005, r=-0.62), and a positive correlation between the number of CD8+ cells and the number of pack years smoked (p=0.017, r=0.42). There was a negative correlation between the activated/total eosinophils ratio and the FEV1 % pred (p=0.017, r=-0.51). There was a negative correlation between pack years smoked and the number of neutrophils (p=0.022, r=-0.36).Smokers who develop chronic obstructive pulmonary disease have increased numbers of CD8+ T-cells in large airways when compared to asymptomatic smokers. Airway obstruction was associated with an increase in the proportion of eosinophils that were activated. Eur Respir J 2000; 15: 512±516.

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Section: Discussionsupporting

confidence: 90%

Subepithelial immunopathology of the large airways in smokers with and without chronic obstructive pulmonary disease

2000

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“…Using this system where purified CD8+ T-cells were stimulated via anti-CD3 and anti-CD28 in the presence or absence of autologous monocytes, we confirmed that the CD103 expression is dependent on TGF-β. Despite the fact that TGF-β is generally considered to inhibit T-cell activation and proliferation, the over all proliferative response to anti-CD3/anti-CD28 stimulation in this system was not markedly decreased by the addition of up to 10 ng/ml of TGF-β 1 elastase. This protease could shift the protease/protease inhibitor imbalance already known to exist in COPD and lead to damage of the epithelium and further inflammation [1] .…”

Section: Discussionmentioning

confidence: 76%

“…The increased numbers of both CD8+ T-cells and monocytes/macrophages in the lungs of COPD patients [1,2] in combination with the increased expression of TGF-β and its correlation to the number of intraepithelial macrophages [16,17] merits a closer study of this particular intra epithelial T-cell population. In fact, it still has to be established whether the presence of these cells is beneficial or detrimental to the disease.…”

Section: Discussionmentioning

confidence: 99%

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αEβ7 Expression on CD8+ T-Cells in COPD BAL Fluid and on TGF-β Stimulated T-Cells In Vitro

Glader

Löfdahl

Wachenfeldt

2005

Lung

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The airway inflammation in patients with COPD shows increased numbers of CD8+ T-cells.Hitherto, few studies have shown any functional data indicating a role for these cells in the pathogenesis of COPD. This paper focuses on a subset of CD8+ T-cells present in human lung, the intra epithelial lymphocytes expressing the integrin αEβ7, and their presence in bronchoalveolar lavage fluid from COPD patients. In this study we demonstrate that 64-89% of the CD8+ T-cells in bronchoalveolar lavage fluid from COPD patients are positive for CD103, the alpha-subunit of αEβ7. We also present an in vitro system in which it is possible to differentiate peripheral T-cells into a phenotype resembling the one found in bronchoalveolar lavage fluid, i.e. CD8+ CD103+. In this in vitro system we demonstrate that, in addition to TGF-β 1 , cell-to-cell interaction between the T-cell and an antigen-presenting cell, here represented by the monocyte, is crucial for a rapid, high and sustained expression of CD103. The signal provided by the monocytes, is shown to be mediated through LFA-1 on the T-cell. Furthermore, differentiation of CD8+ T-cells by TGF-β 1 and monocytes results in down regulation of INF-γ, TNF-α and GM-CSF production. IL-8 production is however retained in the αEβ7 expressing cells. We see this work as an initiation on the quest for a functional characterization of one the different types of CD8+ T cells present in COPD. In the longer perspective we hope this can lead to an increased understanding of how these cells can contribute to the disease pathology.

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“…In addition, the infiltrating macrophages are found to be localised to areas of tissue damage and can express a wide array of proinflammatory mediators (17). Through enhanced secretion of matrix metalloproteinases, e.g., MMP-9/12, alveolar macrophages directly contribute to the tissue destruction observed in emphysema (18).…”

Section: Alveolar Macrophagesmentioning

confidence: 99%

Chronic Obstructive Pulmonary Disease: Evidence for an Autoimmune Component

Stefańska

Walsh

2009

Cell Mol Immunol

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Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible limitation on pulmonary airflow associated with chronic inflammation and mucous hypersecretion (chronic bronchitis) and/or the pathological destruction of alveolar airspaces leading to emphysema. COPD, predominantly as a result of tobacco smoke exposure, represents the fourth leading cause of mortality worldwide and its prevalence is increasing. Despite this, much of the basic mechanisms which contribute to disease progression remain to be elucidated and current therapeutic approaches are, for the most part, based upon alleviating patient symptoms (bronchodilators) as opposed to treating the underlying pathological mechanisms triggered in response to cigarette smoke exposure. The classic disease paradigm suggests that an imbalance of pulmonary matrix proteases versus anti-proteases underlies the tissue destruction and inflammation associated with COPD. However, there is a growing appreciation of the complex and multifaceted nature of the pathological mechanisms associated with disease progression. Recently, there has been mounting evidence indicating that COPD patients exhibit many of the characteristics of a classical autoimmune response. We will discuss current evidence in support of this paradigm and outline how future therapeutic approaches may be tailored to address this. Cellular & Molecular Immunology. 2009;6(2):81-86.

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Alveolar inflammation and its relation to emphysema in smokers.

Cited by 395 publications

References 26 publications

Subepithelial immunopathology of the large airways in smokers with and without chronic obstructive pulmonary disease

Subepithelial immunopathology of the large airways in smokers with and without chronic obstructive pulmonary disease

αEβ7 Expression on CD8+ T-Cells in COPD BAL Fluid and on TGF-β Stimulated T-Cells In Vitro

Chronic Obstructive Pulmonary Disease: Evidence for an Autoimmune Component

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