mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-EOA-2581mimmun-2581Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESВлияние азитромицина на миграцию NK-клеток крови пациентов с хронической обструктивной болезнью легкихEffect of azithromycin on migration of peripheral blood NK cells from patients with chronic obstructive pulmonary diseasehttps://orcid.org/0000-0002-1620-8477КадушкинА. Г.KadushkinA. G.

Кадушкин А.Г. – к.м.н., доцент кафедры биологическойхимии 

220083, г. Минск, пр. Дзержинского, 83

Тел.: 8 (10-37517) 373-93-92

Kadushkin A.G., PhD (Medicine), Associate Professor,Department of Biological Chemistry

83 Dzerzhinski Ave Minsk 220083 Phone: +375 (17) 373-93-92

kadushkyn@gmail.comhttps://orcid.org/0000-0002-0668-2888ТагановичА. Д.TahanovichA. D.

Таганович А.Д. – д.м.н., профессор, заведующийкафедрой биологической химии

Минск

Tahanovich A.D., PhD, MD (Medicine), Professor, Headof the Department of Biological Chemistry

Minsk

taganovich@bsmu.byhttps://orcid.org/0000-0002-0441-0109МовчанЛ. В.MovchanL. V.

Мовчан Л.В. – к.б.н., врач лабораторной диагностики клинико-диагностической лаборатории

 д. Боровляны, Минский р-н

Movchan L.V., PhD (Biology), Doctor of Laboratory Diagnostics, Clinical Diagnostic Laboratory

Borovlyani, Minsk Region

movchan-l@mail.ruhttps://orcid.org/0000-0002-8739-8300ЗафранскаяМ. М.ZafranskayaM. M.

Зафранская М.М. – д.м.н., доцент, заведующая кафедрой иммунологии

Минск

Zafranskaya M.M., PhD, MD (Medicine), Associate Professor, Head, Immunology Department

Minsk

zafranskaya@gmail.comhttps://orcid.org/0000-0001-8669-8005ШманТ. В.ShmanT. V.

Шман Т.В. – к.б.н., заведующая лабораториейиммунологических исследований

 д. Боровляны, Минский р-н

Shman T.V., PhD (Biology), Head, Immunological ResearchLaboratory

Borovlyani, Minsk Region

shman@oncology.byУО «Белорусский государственный медицинский университет»БеларусьBelarusian State Medical UniversityBelarusГУ «Республиканский научно-практический центр детской онкологии, гематологии и иммунологии»БеларусьRepublican Scientific and Practical Center for Pediatric Oncology, Hematology and ImmunologyBelarusУО «Международный государственный экологический институт имени А.Д. Сахарова» Белорусского государственного университетаБеларусьInternational A. Sakharov Environmental Institute, Belarusian State UniversityBelarusГУ "Республиканский научно-практический центр детской онкологии, гематологии и иммунологии"БеларусьRepublican Scientific and Practical Center for Pediatric Oncology, Hematology and ImmunologyBelarus202314112022252309318Copyright © Кадушкин А.Г., Таганович А.Д., Мовчан Л.В., Зафранская М.М., Шман Т.В., 20232023Кадушкин А.Г., Таганович А.Д., Мовчан Л.В., Зафранская М.М., Шман Т.В.Kadushkin A.G., Tahanovich A.D., Movchan L.V., Zafranskaya M.M., Shman T.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2581

До настоящего времени не выявлены лекарственные средства, которые могли бы замедлить неуклонное прогрессирование хронической обструктивной болезни легких (ХОБЛ) или оказали существенное влияние на смертность пациентов. Поэтому продолжаются исследования, направленные на изучение механизмов развития ХОБЛ и поиск препаратов, влияющих на молекулярные звенья его патогенеза. Целью данной работы явилось определить способность комбинации азитромицина и кортикостероидов влиять на миграцию NK-клеток крови пациентов с ХОБЛ. В настоящем исследовании с помощью метода проточной цитометрии определена экспрессия хемокиновых рецепторов CCR5, CCR6, CCR7, CXCR3, CXCR4, CXCR6 на поверхности NK-клеток периферической крови (с фенотипом CD3- CD56+) у 54 курящих пациентов с ХОБЛ, 21 курящего здорового человека и 20 здоровых некурящих лиц. Кроме того, изучено влияние азитромицина (10 мкг/мл) и будесонида (10 нМ) на миграцию NK-клеток пациентов с ХОБЛ (n = 8) к хемокинам CCL5 (10 нМ) и CXCL10 (10 нМ). Установлено, что у курящих пациентов с ХОБЛ по сравнению с курящими здоровыми и некурящими здоровыми людьми в крови повышено процентное содержание NK-клеток, экспрессирующих на своей поверхности хемокиновые рецепторы CXCR3 и CCR5. При этом отсутствуют различия относительного количества этих субпопуляций NK-клеток между здоровыми курильщиками и здоровыми некурящими людьми. Процентное содержание NK-клеток, обладающих хемокиновыми рецепторами CXCR4, CXCR6, CCR6, CCR7, не различается между тремя группами обследованных лиц. Добавление к клеточной суспензии будесонида приводило к снижению миграции NK-клеток крови к хемокинам CCL5 и CXCL10. Азитромицин также подавлял перемещение NK-клеток крови к этим хемокинам. Сочетанное использование азитромицина и будесонида оказывало более выраженное ингибирующее воздействие на хемотаксис NK-клеток к хемокинам CCL5 и CXCL10, чем любой из этих препаратов по отдельности. Полученные результаты свидетельствуют об изменении профиля хемокиновых рецепторов NK-клеток при ХОБЛ и демонстрируют преимущества комбинированного использования глюкокортикоидов и азитромицина для лечения этого заболевания.

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.

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The authors declare that there are no conflicts of interest present.