Endothelial interactions of neutrophils under flow in chronic obstructive pulmonary disease.
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 alpha1-antitrypsin deficiency (PiZ) and neutrophils from 11 COPD patients without the deficiency (PiM). Total adhesive and migratory responses (per mm2 endothelium per 10(6) neutrophils) were significantly greater in the PiM group (mean+/-se 704.2+/-57.9 versus 509.3+/-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+/-se relative fluorescence intensity 1.4+/-0.1 versus 1.1+/-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 alpha1-antitrypsin deficiency, but not in those with severe alpha(1)-antitrypsin deficiency, suggests that this is a predisposing factor for the development of the disease, and upregulation of macrophage antigen-1 may be responsible.
Woolhouse
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IS
Dept of Respiratory Medicine, University Hospital Birmingham, Birmingham B29 6JD, UK. Ian.Woolhouse@uhb.nhs.uk
Bayley
D L
DL
Lalor
P
P
Adams
D H
DH
Stockley
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RA
D000368:Aged; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000276:immunology*