Effect of azithromycin on migration of peripheral blood NK cells from patients with chronic obstructive pulmonary disease

Abstract

Currently, no drugs have been identified that could slow progression of chronic obstructive pulmonary disease (COPD), or have a significant impact on patient mortality. Therefore, research continues aimed at studying the mechanisms of COPD development and searching for drugs that affect its molecular pathogenesis. The aim of our work was to determine the ability of azithromycin combined with corticosteroids to affect the migration of peripheral blood NK cells from the COPD patients. In the present study, we have measured expression of chemokine receptors CCR5, CCR6, CCR7, CXCR3, CXCR4, CXCR6 on the surface of peripheral blood NK cells (CD3- CD56+) by means of flow cytometry in 54 smoking patients with COPD, 21 healthy smokers, and 20 healthy non-smokers. Moreover, the effect of azithromycin (10 µg/mL) and budesonide (10 nM) on the migration of NK cells from COPD patients (n = 8) towards CCL5 (10 nM) and CXCL10 (10 nM) was determined. We found that the percentage of NK cells expressing CXCR3 and CCR5 chemokine receptors was increased in smoking patients with COPD compared with healthy smokers and healthy non-smokers. However, the proportion of these NK cell subsets did not differ between healthy smokers and healthy non-smokers. There were no significant differences in the percentage of NK cells expressing CXCR4, CXCR6, CCR6, CCR7 chemokine receptors between the three groups of subjects. Addition of budesonide to the cell suspensions decreased the migration of blood NK cells towards CCL5 and CXCL10. Azithromycin was also shown to suppress the migration of blood NK cells towards these chemokines. The combination of azithromycin and budesonide was more potent at inhibiting NK cell chemotaxis towards CCL5 and CXCL10 than any of these drugs added alone. Our results demonstrate a change in the chemokine receptor profile of NK cells in COPD patients and indicate the advantages of the combined use of corticosteroids and azithromycin for COPD treatment.