Adhesion molecules in subjects with COPD and healthy non-smokers: a cross sectional parallel group study

Abstract

Background: The aim of the study was to investigate how the expression of adhesion molecules changes as neutrophils migrate from the circulation to the lung and if these changes differ between non-smoking subjects and smokers with and without COPD.

Methods: Non-smoking healthy subjects (n=22), smokers without (n=21) and with COPD (n=18) were included. Neutrophils from peripheral blood, sputum and bronchial biopsies were analysed for cell surface expression of adhesion molecules (CD11b, CD62L, CD162). Serum, sputum supernatant and BAL-fluid were analysed for soluble adhesion molecules (ICAM-1, -3, E-selectin, P-selectin, VCAM-1, PECAM-1).

Results: Expression of CD11b was increased on circulating neutrophils from smokers with COPD. It was also increased on sputum neutrophils in both smokers groups, but not in non-smokers, as compared to circulating neutrophils.Serum ICAM-1 was higher in the COPD group compared to the other two groups (p<0.05) and PECAM-1 was lower in smokers without COPD than in non-smoking controls and the COPD group (p<0.05). In BAL-fluid ICAM-1 was lower in the COPD group than in the other groups (p<0.05).

Conclusions: Thus, our data strongly support the involvement of a systemic component in COPD and demonstrate that in smokers neutrophils are activated to a greater extent at the point of transition from the circulation into the lungs than in non-smokers.

Figure 1

Surface expression of adhesion molecules on blood and sputum neutrophils. Surface expression of A) CD11b, B) CD62L and C) CD162 on blood neutrophils and sputum neutrophils measured by flow cytometry. Results are presented as mean florescence intensity (mfi). P-values indicate comparisons between groups within the same compartment. Cell numbers were not sufficient for flow cytometric analysis in all sputum samples, the analysed numbers are indicated in the figure.

Figure 2

Correlations between lung function and CD11b expression on sputum neutrophils. A: Relation between FEV₁/FVC and CD11b expression in smokers without chronic airflow limitation. B: Relation between disease severity, assessed by FEV₁ in % of predicted value, and CD11b expression.

Figure 3

Soluble adhesion molecules in serum. Levels of soluble adhesion molecules A) ICAM-1, B) ICAM-3, C) PECAM-1, D) VCAM-1, E) E-selectin and F) P-selectin measured in serum from controls (n=12), smokers without COPD (n=12) and smokers with COPD (n=12). Soluble adhesion molecules were measured in subjects where samples from all compartments (blood, sputum and BAL) were available. Results are presented as ng/mL. P-values indicate comparisons between groups.

Figure 4

Expression of adhesion molecules in bronchial biopsies. Co-localisation of neutrophil elastase and A,B) CD11b, C,D) CD62L and E,F) CD162 in bronchial biopsies from a patient with COPD. Neutrophil elastase positive cells are stained in brown; adhesion molecule positive cells are stained in red. Arrows indicate cells double stained cells positive for neutrophil elastase and the respective adhesion molecule. Sections are counterstained with haematoxylin. Original magnification for figure A, C and E is x200 and original magnification for B,E and F is x500.