Integrin Upregulation on Sputum Neutrophils in Smokers with Chronic Airway Obstruction

摘要

To determine the relationship between the expression of leukocyte-specific integrins in the airways and the airway obstruction in smokers, we analyzed hypertonic saline-induced sputum in 33 male subjects, age 64.7 ± 0.5 yr (mean ± SEM), with a smoking history of 12 to 94 pack-years, at the end of a 15-yr follow-up study. Average FEV_1/VC ratio was 69 ± 1% at the beginning of the study and 66 ± 2% at the end of the follow-up period, and annual decline of FEV_1 was 20 ± 3 ml/yr. Fourteen individuals exhibited airway obstruction as assessed by a FEV_1/VC ratio lower than 63.3%. Differential leukocyte count was performed on cytospin preparations and the expression of integrin α (CD11a, CD11b, CD11c) and β (CD18) chains was assessed on granulocytes and mononuclear cells by immunocytol-ogy. The numbers of neutrophils expressing CD11b and CD18, but not CD11c or CD11a, were increased in the subjects with airway obstruction compared with those without airway obstruction. CD11b- and CD18-positive neutrophils were negatively correlated with FEV_1/VC ratio (p < 0.01). No significant correlations were found between CD11a-, CD11b-, CD11c-, CD18-positive mononuclear cells and lung function measurements. In conclusion, our results suggest that leukocyte-specific integrin CD11b/CD18 expressed on sputum polymorphonuclear leukocytes represents a marker for the smokers who develop chronic airway obstruction.