zdorПроблемы здоровья и экологииHealth and Ecology Issues2220-09672708-6011Gomel State Medical University10.51523/2708-6011.2022-19-4-14zdor-2415Research ArticleЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНА И БИОЛОГИЯEXPERIMENTAL MEDICINE AND BIOLOGYИзменение хемотаксиса моноцитов и лимфоцитов крови пациентов с хронической обструктивной болезнью легких под влиянием будесонида и азитромицинаEffect of budesonide and azithromycin on the chemotaxis of blood monocytes and lymphocytes in patients with chronic obstructive pulmonary diseasehttps://orcid.org/0000-0002-1620-8477КадушкинА. Г.KadushkinA. G.

Кадушкин Алексей Геннадьевич, к.м.н., доцент кафедры биологической химии

Минск

Aliaksei G. Kadushkin, Candidate of Medical Sciences,Associate Professor at the Department of Biological Chemistry

Minsk

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

Таганович Анатолий Дмитриевич, д.м.н., профессор,заведующий кафедрой биологической химии

Минск

Anatoli D. Tahanovich, Doctor of Medical Sciences,Professor, Head of the Department of Biological Chemistry

Minsk

taganovich@bsmu.byhttps://orcid.org/0000-0002-2961-0465КолесниковаТ. С.KolesnikovaT. S.

Колесникова Татьяна Сергеевна, старший научныйсотрудник лаборатории биохимических методов исследования

Минск

Tatsiana S. Kolesnikova, Senior Researcher of theLaboratory of Biochemical Research Methods

Minsk

tanyakolesnikova@list.ruhttps://orcid.org/0000-0003-0840-6729ХодосовскаяЕ. В.KhadasouskayaA. V.

Ходосовская Елена Вячеславовна, старший научныйсотрудник лаборатории биохимических методов исследования

Минск

Alena V. Khadasouskaya, Senior Researcher of theLaboratory of Biochemical Research Methods

Minsk

leno4ka_579@mail.ruБелорусский государственный медицинский университетBelarusian State Medical University202204012023194103110Copyright © Кадушкин А.Г., Таганович А.Д., Колесникова Т.С., Ходосовская Е.В., 20232023Кадушкин А.Г., Таганович А.Д., Колесникова Т.С., Ходосовская Е.В.Kadushkin A.G., Tahanovich A.D., Kolesnikova T.S., Khadasouskaya A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.gsmu.by/jour/article/view/2415Цель исследования

Цель исследования. Оценить способность комбинации будесонида и азитромицина влиять на миграцию моноцитов и лимфоцитов крови пациентов с хронической обструктивной болезнью легких (ХОБЛ).

Материалы и методы

Материалы и методы. Мононуклеарные клетки периферической крови пациентов с ХОБЛ (n = 8) инкубировали с глюкокортикоидом будесонидом (10 нM), макролидным антибиотиком азитромицином (10 мкг/мл) или их комбинацией, после чего переносили в миграционные планшеты, содержащие хемокины RANTES (CCL5, 10 нМ) или IP-10 (CXCL10, 10 нМ). Клетки, мигрировавшие в нижнюю камеру планшета, собирали, окрашивали моноклональными антителами к CD3, СD14, CD19, CD45 и подсчитывали на проточном цитометре.

Результаты

Результаты. Азитромицин самостоятельно и в сочетании с будесонидом подавлял миграцию Т-лимфоцитов и B-клеток крови и ускорял перемещение моноцитов крови к RANTES и IP-10. Комбинация азитромицина и будесонида обладала более супрессирующим действием на хемотаксис Т- и B-лимфоцитов крови к RANTES и IP-10, чем один будесонид. Сочетание азитромицина и будесонида оказывало действие, схожее с влиянием одного азитромицина, на миграцию Т- и В-лимфоцитов, а также моноцитов крови пациентов с ХОБЛ.

Заключение

Заключение. Результаты исследования демонстрируют способность азитромицина самостоятельно модулировать хемотаксис моноцитов и лимфоцитов периферической крови пациентов с ХОБЛ и отсутствие преимуществ его комбинации с будесонидом.

Objective

Objective. To evaluate the ability of a combination of budesonide and azithromycin to influence the migration of blood monocytes and lymphocytes in patients with chronic obstructive pulmonary disease (COPD).

Materials and methods

Materials and methods. Peripheral blood mononuclear cells from patients with COPD (n=8) were incubated with glucocorticoid budesonide (10 nM), macrolide antibiotic azithromycin (10 µg/mL), or their combination, and then transferred to chemotaxis chambers containing chemokines RANTES (CCL5, 10 nM) or IP-10 (CXCL10, 10 nM). Cells migrated to the lower compartment of the chamber were collected, stained with monoclonal antibodies to CD3, CD14, CD19, CD45 and counted on a flow cytometer.

Results

Results. Azithromycin alone and in combination with budesonide inhibited the migration of blood T-lymphocytes and B-cells and enhanced the migration of blood monocytes to RANTES and IP-10. The combination of azithromycin and budesonide had a more suppressive effect on the chemotaxis of blood T- and B-lymphocytes to RANTES and IP-10 than budesonide alone. The combination of azithromycin and budesonide had an effect similar to azithromycin alone on the migration of blood T- and B-lymphocytes, as well as monocytes in patients with COPD.

Conclusion

Conclusion. The results of the study demonstrate the ability of azithromycin alone to modulate the chemotaxis of peripheral blood monocytes and lymphocytes in patients with COPD and the lack of advantages of its combination with budesonide.

хемотаксисазитромицинбудесонидмоноцитылимфоцитыхроническая обструктивная болезнь легкихchemotaxisazithromycinbudesonidemonocyteslymphocytesCOPDРабота выполнена при финансовой поддержке государственной программы научных исследований (ГПНИ) «Фундаментальные и прикладные науки — медицине» в рамках задания № 2.56.ReferencesBarnes PJ. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2016 Jul;138(1):16-27. DOI: https://doi.org/10.1016/j.jaci.2016.05.011Barnes PJ. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2016 Jul;138(1):16-27. DOI: https://doi.org/10.1016/j.jaci.2016.05.011Solidoro P, Albera C, Ribolla F, Bellocchia M, Brussino L, Patrucco F. Triple Therapy in COPD: Can We Welcome the Reduction in Cardiovascular Risk and Mortality? Front Med (Lausanne). 2022 Mar 23;9:816843. DOI: https://doi.org/10.3389/fmed.2022.816843Solidoro P, Albera C, Ribolla F, Bellocchia M, Brussino L, Patrucco F. Triple Therapy in COPD: Can We Welcome the Reduction in Cardiovascular Risk and Mortality? Front Med (Lausanne). 2022 Mar 23;9:816843. DOI: https://doi.org/10.3389/fmed.2022.816843Wang Y, Xu J, Meng Y, Adcock IM, Yao X. Role of inflammatory cells in airway remodeling in COPD. Int J Chron Obstruct Pulmon Dis. 2018 Oct 12;13:3341-3348. DOI: https://doi.org/10.2147/COPD.S176122Wang Y, Xu J, Meng Y, Adcock IM, Yao X. Role of inflammatory cells in airway remodeling in COPD. Int J Chron Obstruct Pulmon Dis. 2018 Oct 12;13:3341-3348. DOI: https://doi.org/10.2147/COPD.S176122Кадушкин АГ, Таганович АД, Мовчан ЛВ, Зафранская ММ, Дядичкина ОВ, Шман ТВ. Популяционная перестройка B-лимфоцитов, экспрессирующих хемокиновые рецепторы, у пациентов с хронической обструктивной болезнью легких. Биомедицинская химия. 2022;68(2):134-143. DOI: https://doi.org/10.18097/PBMC20226802134Kadushkin AG, Tahanovich AD, Movchan LV, Zafranskaya MM, Dziadzichkina VV, Shman TV. Population rearrangement of B-lymphocytes expressing chemokine receptors in patients with chronic obstructive pulmonary disease. Biomed Khim. 2022;68(2):134-143. (In Russ.). DOI: https://doi.org/10.18097/PBMC20226802134Henrot P, Prevel R, Berger P, Dupin I. Chemokines in COPD: From Implication to Therapeutic Use. Int J Mol Sci. 2019 Jun 6;20(11):2785. DOI: https://doi.org/10.3390/ijms20112785Henrot P, Prevel R, Berger P, Dupin I. Chemokines in COPD: From Implication to Therapeutic Use. Int J Mol Sci. 2019 Jun 6;20(11):2785. DOI: https://doi.org/10.3390/ijms20112785Tashkin DP, Strange C. Inhaled corticosteroids for chronic obstructive pulmonary disease: what is their role in therapy? Int J Chron Obstruct Pulmon Dis. 2018 Aug 27;13:2587-2601. DOI: https://doi.org/10.2147/COPD.S172240Tashkin DP, Strange C. Inhaled corticosteroids for chronic obstructive pulmonary disease: what is their role in therapy? Int J Chron Obstruct Pulmon Dis. 2018 Aug 27;13:2587-2601. DOI: https://doi.org/10.2147/COPD.S172240Kadushkin A, Tahanovich A, Movchan L, Talabayeva E, Plastinina A, Shman T. Azithromycin modulates release of steroid-insensitive cytokines from peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease. Adv Respir Med. 2022 Jan 24;90(1):17-27. DOI: https://doi.org/10.5603/ARM.a2022.0002Kadushkin A, Tahanovich A, Movchan L, Talabayeva E, Plastinina A, Shman T. Azithromycin modulates release of steroid-insensitive cytokines from peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease. Adv Respir Med. 2022 Jan 24;90(1):17-27. DOI: https://doi.org/10.5603/ARM.a2022.0002Kobayashi Y, Wada H, Rossios C, Takagi D, Charron C, Barnes PJ, et al. A novel macrolide/fluoroketolide, solithromycin (CEM-101), reverses corticosteroid insensitivity via phosphoinositide 3-kinase pathway inhibition. Br J Pharmacol. 2013 Jul;169(5):1024-1034. DOI: https://doi.org/10.1111/bph.12187Kobayashi Y, Wada H, Rossios C, Takagi D, Charron C, Barnes PJ, et al. A novel macrolide/fluoroketolide, solithromycin (CEM-101), reverses corticosteroid insensitivity via phosphoinositide 3-kinase pathway inhibition. Br J Pharmacol. 2013 Jul;169(5):1024-1034. DOI: https://doi.org/10.1111/bph.12187Oliver ME, Hinks TSC. Azithromycin in viral infections. Rev Med Virol. 2021 Mar;31(2):e2163. DOI: https://doi.org/10.1002/rmv.2163Oliver ME, Hinks TSC. Azithromycin in viral infections. Rev Med Virol. 2021 Mar;31(2):e2163. DOI: https://doi.org/10.1002/rmv.2163Kong FY, Rupasinghe TW, Simpson JA, Vodstrcil LA, Fairley CK, McConville MJ, et al. Pharmacokinetics of a single 1g dose of azithromycin in rectal tissue in men. PLoS One. 2017 Mar 28;12(3):e0174372. DOI: https://doi.org/10.1371/journal.pone.0174372Kong FY, Rupasinghe TW, Simpson JA, Vodstrcil LA, Fairley CK, McConville MJ, et al. Pharmacokinetics of a single 1g dose of azithromycin in rectal tissue in men. PLoS One. 2017 Mar 28;12(3):e0174372. DOI: https://doi.org/10.1371/journal.pone.0174372Stellari FF, Sala A, Donofrio G, Ruscitti F, Caruso P, Topini TM, et al. Azithromycin inhibits nuclear factor-κB activation during lung inflammation: an in vivo imaging study. Pharmacol Res Perspect. 2014 Oct;2(5):e00058. DOI: https://doi.org/10.1002/prp2.58Stellari FF, Sala A, Donofrio G, Ruscitti F, Caruso P, Topini TM, et al. Azithromycin inhibits nuclear factor-κB activation during lung inflammation: an in vivo imaging study. Pharmacol Res Perspect. 2014 Oct;2(5):e00058. DOI: https://doi.org/10.1002/prp2.58Haydar D, Cory TJ, Birket SE, Murphy BS, Pennypacker KR, Sinai AP, et al. Azithromycin Polarizes Macrophages to an M2 Phenotype via Inhibition of the STAT1 and NF-κB Signaling Pathways. J Immunol. 2019 Aug 15;203(4):1021-1030. DOI: https://doi.org/10.4049/jimmunol.1801228Haydar D, Cory TJ, Birket SE, Murphy BS, Pennypacker KR, Sinai AP, et al. Azithromycin Polarizes Macrophages to an M2 Phenotype via Inhibition of the STAT1 and NF-κB Signaling Pathways. J Immunol. 2019 Aug 15;203(4):1021-1030. DOI: https://doi.org/10.4049/jimmunol.1801228Bosnar M, Čužić S, Bošnjak B, Nujić K, Ergović G, Marjanović N, et al. Azithromycin inhibits macrophage interleukin1β production through inhibition of activator protein-1 in lipopolysaccharide-induced murine pulmonary neutrophilia. Int Immunopharmacol. 2011 Apr;11(4):424-434. DOI: https://doi.org/10.1016/j.intimp.2010.12.010Bosnar M, Čužić S, Bošnjak B, Nujić K, Ergović G, Marjanović N, et al. Azithromycin inhibits macrophage interleukin1β production through inhibition of activator protein-1 in lipopolysaccharide-induced murine pulmonary neutrophilia. Int Immunopharmacol. 2011 Apr;11(4):424-34. DOI: https://doi.org/10.1016/j.intimp.2010.12.010Khezri MR, Zolbanin NM, Ghasemnejad-Berenji M, Jafari R. Azithromycin: Immunomodulatory and antiviral properties for SARS-CoV-2 infection. Eur J Pharmacol. 2021 Aug 15;905:174191. DOI: https://doi.org/10.1016/j.ejphar.2021.174191Khezri MR, Zolbanin NM, Ghasemnejad-Berenji M, Jafari R. Azithromycin: Immunomodulatory and antiviral properties for SARS-CoV-2 infection. Eur J Pharmacol. 2021 Aug 15;905:174191. DOI: https://doi.org/10.1016/j.ejphar.2021.174191Kuo CH, Lee MS, Kuo HF, Lin YC, Hung CH. Azithromycin suppresses Th1- and Th2-related chemokines IP10/MDC in human monocytic cell line. J Microbiol Immunol Infect. 2019 Dec;52(6):872-879. DOI: https://doi.org/10.1016/j.jmii.2019.10.001Kuo CH, Lee MS, Kuo HF, Lin YC, Hung CH. Azithromycin suppresses Th1- and Th2-related chemokines IP10/MDC in human monocytic cell line. J Microbiol Immunol Infect. 2019 Dec;52(6):872-879. DOI: https://doi.org/10.1016/j.jmii.2019.10.001Singh D, Agusti A, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur Respir J. 2019 May 18;53(5):1900164. DOI: https://doi.org/10.1183/13993003.00164-2019Singh D, Agusti A, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur Respir J. 2019 May 18;53(5):1900164. DOI: https://doi.org/10.1183/13993003.00164-2019Moe KT, Khairunnisa K, Yin NO, Chin-Dusting J, Wong P, Wong MC. Tumor necrosis factor-α-induced nuclear factorkappaB activation in human cardiomyocytes is mediated by NADPH oxidase. J Physiol Biochem. 2014 Sep;70(3):769-79. DOI: https://doi.org/10.1007/s13105-014-0345-0Moe KT, Khairunnisa K, Yin NO, Chin-Dusting J, Wong P, Wong MC. Tumor necrosis factor-α-induced nuclear factorkappaB activation in human cardiomyocytes is mediated by NADPH oxidase. J Physiol Biochem. 2014 Sep;70(3):769-79. DOI: https://doi.org/10.1007/s13105-014-0345-0Caramori G, Casolari P, Barczyk A, Durham AL, Di Stefano A, Adcock I. COPD immunopathology. Semin Immunopathol. 2016 Jul;38(4):497-515. DOI: https://doi.org/10.1007/s00281-016-0561-5Caramori G, Casolari P, Barczyk A, Durham AL, Di Stefano A, Adcock I. COPD immunopathology. Semin Immunopathol. 2016 Jul;38(4):497-515. DOI: https://doi.org/10.1007/s00281-016-0561-5Barnes PJ. Targeting cytokines to treat asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. 2018 Jul;18(7):454-466. DOI: https://doi.org/10.1038/s41577-018-0006-6Barnes PJ. Targeting cytokines to treat asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. 2018 Jul;18(7):454-466. DOI: https://doi.org/10.1038/s41577-018-0006-6Honda K, Wada H, Nakamura M, Nakamoto K, Inui T, Sada M, et al. IL-17A synergistically stimulates TNF-α-induced IL-8 production in human airway epithelial cells: A potential role in amplifying airway inflammation. Exp Lung Res. 2016 May;42(4):205-216. DOI: https://doi.org/10.1080/01902148.2016.1190796Honda K, Wada H, Nakamura M, Nakamoto K, Inui T, Sada M, et al. IL-17A synergistically stimulates TNF-α-induced IL-8 production in human airway epithelial cells: A potential role in amplifying airway inflammation. Exp Lung Res. 2016 May;42(4):205-216. DOI: https://doi.org/10.1080/01902148.2016.1190796Yuan S, Zhang S, Zhuang Y, Zhang H, Bai J, Hou Q. Interleukin-17 Stimulates STAT3-Mediated Endothelial Cell Activation for Neutrophil Recruitment. Cell Physiol Biochem. 2015;36(6):2340-2356. DOI: https://doi.org/10.1159/000430197Yuan S, Zhang S, Zhuang Y, Zhang H, Bai J, Hou Q. Interleukin-17 Stimulates STAT3-Mediated Endothelial Cell Activation for Neutrophil Recruitment. Cell Physiol Biochem. 2015;36(6):2340-2356. DOI: https://doi.org/10.1159/000430197Polverino F, Seys LJ, Bracke KR, Owen CA. B cells in chronic obstructive pulmonary disease: moving to center stage. Am J Physiol Lung Cell Mol Physiol. 2016 Oct 1;311(4):L687-L695. DOI: https://doi.org/10.1152/ajplung.00304.2016Polverino F, Seys LJ, Bracke KR, Owen CA. B cells in chronic obstructive pulmonary disease: moving to center stage. Am J Physiol Lung Cell Mol Physiol. 2016 Oct 1;311(4):L687-L695. DOI: https://doi.org/10.1152/ajplung.00304.2016Kato A, Hulse KE, Tan BK, Schleimer RP. B-lymphocyte lineage cells and the respiratory system. J Allergy Clin Immunol. 2013 Apr;131(4):933-957. DOI: https://doi.org/10.1016/j.jaci.2013.02.023Kato A, Hulse KE, Tan BK, Schleimer RP. B-lymphocyte lineage cells and the respiratory system. J Allergy Clin Immunol. 2013 Apr;131(4):933-957. DOI: https://doi.org/10.1016/j.jaci.2013.02.023Ehrchen JM, Roth J, Barczyk-Kahlert K. More Than Suppression: Glucocorticoid Action on Monocytes and Macrophages. Front Immunol. 2019 Aug 27;10:2028. DOI: https://doi.org/10.3389/fimmu.2019.02028Ehrchen JM, Roth J, Barczyk-Kahlert K. More Than Suppression: Glucocorticoid Action on Monocytes and Macrophages. Front Immunol. 2019 Aug 27;10:2028. DOI: https://doi.org/10.3389/fimmu.2019.02028

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