The expression of adhesion molecules in cigarette smoke-induced airways obstruction

González, Shirley; Hards, Jennifer; Eeden, Stephan Van; Hogg, James C.

doi:10.1183/09031936.96.09101995

Cited by 39 publications

(29 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The evidence for this derives from studies demonstrating an increased number of inflammatory cells (10,14,19), their activation status (20), and the release of putative proinflammatory mediators (21). In our study we have demonstrated an increased number of leukocytes infiltrating the adventitia of pulmonary muscular arteries in COPD patients, largely constituted by activated T lymphocytes.…”

Section: Discussionmentioning

confidence: 56%

Inflammatory Reaction in Pulmonary Muscular Arteries of Patients with Mild Chronic Obstructive Pulmonary Disease

Peinado

Barberà

Abate

et al. 1999

Am J Respir Crit Care Med

251

187

View full text Add to dashboard Cite

Endothelial dysfunction and intimal thickening have been shown in pulmonary arteries (PA) of patients with mild chronic obstructive pulmonary disease (COPD). To investigate whether an inflammatory process related to tobacco smoking might be involved in the development of pulmonary vascular abnormalities in COPD, we characterized the inflammatory cell infiltrate and the endothelium-dependent relaxation in PA of 39 patients who underwent lung resection, divided into three groups: "nonsmokers" (n ϭ 7); "smokers," with normal lung function (n ϭ 12); and "COPD" (n ϭ 20). Endothelium-dependent relaxation was assessed in vitro by exposing PA rings to adenosine diphosphate (ADP). Inflammatory cell types were identified by immunohistochemistry. PA of COPD patients Structural and functional abnormalities of the pulmonary circulation are common features in the wide spectrum of chronic obstructive pulmonary disease (COPD). Dysfunction of the pulmonary endothelium, which is associated with an impaired release of endothelium-derived nitric oxide (NO), may play a critical role in the remodeling of pulmonary vessels in COPD. Endothelial dysfunction in pulmonary arteries was initially shown in end-stage COPD patients undergoing lung transplantation by Dinh-Xuan and coworkers (1). In a recent study we observed that endothelial dysfunction may also be present in pulmonary arteries of patients with mild COPD (2). However, whereas in end-stage COPD chronic severe hypoxemia may account for the impairment of the endothelial function (1), the mechanisms of such an impairment in patients with milder degrees of disease, who are not hypoxemic, are unknown.Several studies performed in lungs of patients with mild COPD have shown apparent abnormalities in the structure of the pulmonary muscular arteries, in most cases consisting of the thickening of the intimal layer (3-5). Interestingly, the intensity of the intimal thickening has been shown to correlate with the severity of the inflammatory infiltrate in small airways (5, 6), suggesting that an inflammatory process might also account for the structural abnormalities of the pulmonary artery wall. Indeed, inflammation has been shown to be involved in the pathogenesis of some forms of pulmonary hypertension (7) and also in the remodeling of systemic vessels (8). Accordingly, we hypothesized that the structural abnormalities and the endothelial dysfunction shown in pulmonary arteries of patients with mild COPD could be related to an inflammatory process.Cigarette smoking causes an inflammatory reaction in the airways of patients with COPD. Whereas in both asymptomatic smokers and patients with COPD the nature and characteristics of the inflammatory reaction in central and peripheral airways (9-14), as well as in alveolar septa (15), have been thoroughly evaluated, little is known about the degree, nature, and evolution of the inflammatory infiltrate in pulmonary arteries of COPD patients.The present study, results of which have been given in abstract form (16), was therefore addressed to inves...

show abstract

Section: Discussionmentioning

confidence: 56%

Inflammatory Reaction in Pulmonary Muscular Arteries of Patients with Mild Chronic Obstructive Pulmonary Disease

Peinado

Barberà

Abate

et al. 1999

Am J Respir Crit Care Med

251

187

View full text Add to dashboard Cite

show abstract

“…Furthermore, bloodflow through vessels subjects endothelial cells to shear stress, which can elicit cytoskeletal remodelling and activation of natural signalling cascades in endothelial cells, including the activation of nuclear factor-kB and upregulation of intracellular adhesion molecule (ICAM)-1 [15]. The flow-based assay used in the current study incorporates these aspects and, when used in conjunction with HUVEC, which have a similar adhesion molecule profile (following IL-1b stimulation) to that seen on bronchial post-capillary venules [10,11], provides an appropriate model of neutrophil-endothelial cell interactions in the airways of patients with COPD.…”

Section: Discussionmentioning

confidence: 99%

“…Cells were not used beyond their sixth passage. HUVEC were chosen for this study because of the ease of culture to confluence within the glass microslide, and the similar profile of adhesion molecule expression following interleukin (IL)-1b stimulation to that seen on postcapillary venules in the bronchial circulation of smokers [10,11].…”

Section: Study Populationsmentioning

confidence: 99%

See 1 more Smart Citation

Endothelial interactions of neutrophils under flow in chronic obstructive pulmonary disease

Woolhouse¹

2005

Eur Respir J

View full text Add to dashboard Cite

It is generally accepted that the neutrophil is central to the pathogenesis of chronic obstructive pulmonary disease (COPD). Enhanced endothelial interactions of this cell may contribute to the susceptibility of smokers who develop the disease; however, these interactions have not previously been studied in COPD. The aim of the current study was to determine whether enhanced endothelial interactions of neutrophils from smokers are a predisposing factor for the development of COPD.Endothelial interactions under flow and adhesion molecule expression of peripheral blood neutrophils were compared between seven never-smokers (NS), seven healthy smokers (HS), 11 COPD patients with severe α1-antitrypsin deficiency (PiZ) and neutrophils from 11 COPD patients without the deficiency (PiM).Total adhesive and migratory responses (per mm2endothelium per 106neutrophils) were significantly greater in the PiM group (mean±se704.2±57.9versus509.3±48.8 in the PiZ group, 499.3±40.1 in the HS and 491.2±33.7 in the NS). This corresponded with increased macrophage antigen-1 (CD11b) expression on stimulated neutrophils in the PiM group compared with the PiZ group (mean±serelative fluorescence intensity 1.4±0.1versus1.1±0.1).In conclusion, the enhanced endothelial interaction of neutrophils from smokers who have developed chronic obstructive pulmonary disease in the presence of normal levels of α1-antitrypsin deficiency, but not in those with severe α1-antitrypsin deficiency, suggests that this is a predisposing factor for the development of the disease, and upregulation of macrophage antigen-1 may be responsible.

show abstract

“…The expression of macrophage associated antigen-1 (Mac-1) is increased on neutrophils of patients with stable COPD, suggesting that targeting such adhesion molecules may have therapeutic potential (Noguera et al 1998). The expression of leukocyte as well as epithelial/endothelial surface adhesion molecules was elevated in resected lung tissue from heavy smokers, consistent with an infl ammatory response to lung infl ammation but not correlated to the degree of airways obstruction (Gonzalez et al 1996). Increased levels of circulating intercellular adhesion molecule-1 (cICAM-1) and circulating E-selectin (c-E-selectin) in serum, and of cICAM-1 in BAL, were observed in COPD patients relative to controls.…”

Section: Adhesion Moleculesmentioning

confidence: 75%

Identifying targets for COPD treatment through gene expression analyses

Chen¹,

Kim²,

Ryter³

et al. 2008

COPD

View full text Add to dashboard Cite

Despite the status of chronic obstructive pulmonary disease (COPD) as a major global health problem, no currently available therapies can limit COPD progression. Therefore, an urgent need exists for the development of new and effective treatments for COPD. An improved understanding in the molecular pathogenesis of COPD can potentially identify molecular targets to facilitate the development of new therapeutic modalities. Among the best approaches for understanding the molecular basis of COPD include gene expression profi ling techniques, such as serial analysis of gene expression or microarrays. Using these methods, recent studies have mapped comparative gene expression profi les of lung tissues from patients with different stages of COPD relative to healthy smokers or non-smokers. Such studies have revealed a number of differentially-regulated genes associated with COPD progression, which include genes involved in the regulation of infl ammation, extracellular matrix, cytokines, chemokines, apoptosis, and stress responses. These studies have shed new light on the molecular mechanisms of COPD, and suggest novel targets for clinical treatments.

show abstract

The expression of adhesion molecules in cigarette smoke-induced airways obstruction

Cited by 39 publications

References 25 publications

Inflammatory Reaction in Pulmonary Muscular Arteries of Patients with Mild Chronic Obstructive Pulmonary Disease

Inflammatory Reaction in Pulmonary Muscular Arteries of Patients with Mild Chronic Obstructive Pulmonary Disease

Endothelial interactions of neutrophils under flow in chronic obstructive pulmonary disease

Identifying targets for COPD treatment through gene expression analyses

Contact Info

Product

Resources

About