vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1814-6023-2023-20-3-191-204vestim-926Research ArticleКЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАCLINICAL AND EXPERIMENTAL MEDICINEМиграция Т-лимфоцитов крови пациентов с хронической обструктивной болезнью легких к хемокинам RANTES и IP-10 под влиянием азитромицинаImpact of azithromycin on the migration of peripheral blood T lymphocytes from patients with chronic obstructive pulmonary disease to RANTES and IP-10https://orcid.org/0000-0002-1620-8477КадушкинА. Г.KadushkinA. G.

Кадушкин Алексей Геннадьевич – кандидат медицинских наук, доцент.

пр. Дзержинского, 83, 220083, Минск

Aliaksei G. Kadushkin – Ph. D. (Med.), Associate Professor, Belarusian State Medical University.

83, Dzerzhinski Ave., 220083, Minsk

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

Таганович Анатолий Дмитриевич – доктор медицинских наук, профессор, заведующий кафедрой.

пр. Дзержинского, 83, 220083, Минск

Anatoli D. Tahanovich – D. Sc. (Med.), Professor, Head of the Department, Belarusian State Medical University.

83, Dzerzhinski Ave., 220083, Minsk

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

Мовчан Людмила Викторовна – кандидат биологических наук, врач лабораторной диагностики.

ул. Фрунзенская, 43, 223053, д. Боровляны, Минский р-н

Lyudmila V. Movchan – Ph. D. (Biol.), Doctor of Laboratory Diagnostics, Republican Scientific and Practical Center for Pediatric Oncology, Hematology and Immunology.

43, Frunzenskaya Str., 223053, Borovliany, Minsk region

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

Зафранская Марина Михайловна – доктор медицинских наук, доцент, заведующий кафедрой.

ул. Долгобродская, 23/1, 220070, Минск

Marina M. Zafranskaya – D. Sc. (Med.), Associate Professor, Head of the Department, International Sakharov Environmental Institute of Belarusian State University.

23/1, Dolgobrodskaya Str., 220070, Minsk

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

Шман Татьяна Викторовна – кандидат биологических наук, заведующий лабораторией.

ул. Фрунзенская, 43, 223053, д. Боровляны, Минский р-н

Tatsiana V. Shman – Ph. D. (Biol.), Head of the Laboratory, Republican Scientific and Practical Center for Pediatric Oncology, Hematology and Immunology.

43, Frunzenskaya Str., 223053, Borovliany, Minsk region

shman@oncology.byБелорусский государственный медицинский университетBelarusian State Medical UniversityРеспубликанский научно-практический центр детской онкологии, гематологии и иммунологииRepublican Scientific and Practical Center for Pediatric Oncology, Hematology and ImmunologyМеждународный государственный экологический институт имени А. Д. Сахарова Белорусского государственного университетаInternational Sakharov Environmental Institute of Belarusian State University202301092023203191204Copyright © 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://vestimed.belnauka.by/jour/article/view/926

Характерный для хронической обструктивной болезни легких (ХОБЛ) воспалительный процесс сопровождается миграцией Т-лимфоцитов из крови в дыхательные пути. Подавление хемотаксиса T-клеток с помощью лекарственных средств может ослабить воспалительную реакцию у пациентов с ХОБЛ.

Целью настоящего исследования являлось определение способности комбинации азитромицина и глюкокортикоидов влиять на миграцию T-клеток крови пациентов с ХОБЛ.

Процентное содержание Т-лимфоцитов, экспрессирующих хемокиновые рецепторы CCR5, CCR6, CCR7, CXCR3, CXCR4, CXCR6, анализировали методом проточной цитометрии в периферической крови 54 курящих пациентов с ХОБЛ, 21 курящего здорового человека и 20 здоровых некурящих лиц, а также в бронхоальвеолярной лаважной жидкости (БАЛЖ) 7 курящих пациентов с ХОБЛ и 7 здоровых курильщиков. Дополнительно определяли миграцию Т-хелперов и цитотоксических Т-лимфоцитов крови пациентов с ХОБЛ (n = 8) к хемокинам RANTES (10 нМ) и IP-10 (10 нМ) при их инкубации с азитромицином (10 мкг/мл) и будесонидом (10 нМ).

Проведенные исследования показали повышение процентного содержания Т-лимфоцитов, экспрессирующих хемокиновые рецепторы CXCR3 и CCR5, в периферической крови курящих пациентов с ХОБЛ по сравнению с таковым у здоровых курильщиков и здоровых некурящих людей, а также в БАЛЖ курящих пациентов с ХОБЛ по сравнению с аналогичным показателем у здоровых курящих людей. В периферической крови и БАЛЖ показатели относительного количества Т-клеток, содержащих хемокиновые рецепторы CXCR4, CXCR6, CCR6 и CCR7, не различались у пациентов с ХОБЛ и здоровых людей. Будесонид подавлял только миграцию цитотоксических Т-лимфоцитов к RANTES. Азитромицин самостоятельно и в сочетании с будесонидом ингибировал миграцию Т-хелперов и цитотоксических Т-лимфоцитов крови в направлении RANTES и IP-10. При этом способность азитромицина супрессировать миграцию T-клеток в комбинации с будесонидом и без него превосходила эффективность одного будесонида.

Полученные данные свидетельствуют о значении рецепторов CXCR3 и CCR5 в привлечении Т-клеток в легкие пациентов с ХОБЛ и демонстрируют способность азитромицина ингибировать миграцию Т-лимфоцитов.

The inflammatory process specific for chronic obstructive pulmonary disease (COPD) is accompanied by T lymphocyte migration from peripheral blood to the respiratory tract. Suppression of T cell chemotaxis by drugs may attenuate the inflammatory response in patients with COPD.

The aim of this study was to determine the ability of azithromycin in combination with glucocorticoids to affect the migration of blood T cells in patients with COPD.

The percentage of T lymphocytes expressing chemokine receptors CCR5, CCR6, CCR7, CXCR3, CXCR4, CXCR6 was analyzed by flow cytometry in the peripheral blood of 54 smokers with COPD, 21 healthy smokers, and 20 healthy non-smokers, as well as in bronchoalveolar lavage (BAL) of 7 smokers with COPD and 7 healthy smokers. Additionally, we determined the effect of azithromycin (10 μg/ml) and budesonide (10 nM) on the migration of peripheral blood T helper cells and cytotoxic T lymphocytes from patients with COPD (n = 8) to chemokines RANTES (10 nM) and IP-10 (10 nM).

The percentage of T lymphocytes expressing chemokine receptors CXCR3 and CCR5 increased in the peripheral blood of COPD smokers compared with healthy smokers and healthy non-smokers, as well as in the BAL of COPD smokers compared with healthy smokers. The proportion of T cells expressing chemokine receptors CXCR4, CXCR6, CCR6, and CCR7 did not differ in the peripheral blood and the BAL between COPD patients and healthy controls. Budesonide only inhibited the migration of cytotoxic T lymphocytes to RANTES. Azithromycin, alone and combined with budesonide, inhibited the migration of T helper cells and cytotoxic T lymphocytes to both RANTES and IP-10. Moreover, the inhibitory effect of azithromycin, in combination with budesonide and without it, on the T cell migration was significantly greater than the effect of budesonide alone.

Our results suggest a role for CXCR3 and CCR5 in T cell recruitment into the lungs of COPD patients and demonstrate the ability of azithromycin to inhibit T lymphocyte migration.

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