Endothelial interactions of neutrophils under flow in chronic obstructive pulmonary disease

Abstract

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.

Variability of sputum inflammatory mediators in COPD and α1-antitrypsin deficiency

“…There is evidence of aberrant neutrophil migration in usual COPD [42], which is not present in A1ATD [43,44], and differences in the adherence and speed of migrating neutrophils in COPD could, theoretically, lead to an increased neutrophil presence and degranulation in the airways, despite lower concentrations of chemoattractants, potentially explaining the lower neutrophil numbers in A1ATD despite higher chemoattractant concentrations.…”

Aberrant neutrophil functions in stable chronic obstructive pulmonary disease: The neutrophil as an immunotherapeutic target

“…A number of studies suggest that neutrophils from patients with COPD display increased adhesion and migration towards inflammatory stimuli [48][49][50], although this has not been universally replicated [51]. These studies provide information on bulk cell movement towards a chemo-attractant at the end of a given timeframe.…”

The neutrophil in chronic obstructive pulmonary disease

“…Upregulation of neutrophil adhesion molecules such as CD621 and macrophage antigen (MAC)-1 (CD11b/CD18) increases neutrophil-endothelial cell interaction. 7 In patients with COPD, neutrophils have been shown to have increased surface expression of MAC-1. 8 This is important, because it is thought MAC-1 (CD11b/CD18) facilitates neutrophil adhesion via its endothelial counter receptor intercellular adhesion molecule 1 (ICAM-1).…”