mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-DOP-1890mimmun-1890Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESЗависимость фенотипа и хемилюминесцентной активности моноцитов от количества Т-регуляторных клеток у больных раком почкиDependence of phenotype and chemiluminescent activity of monocytes on the Tregulatory cells content in patients with kidney cancerСавченкоА. А.SavchenkoA. A.

Савченко Андрей Анатольевич — докторр медицинских наук, профессор, руководитель лаборатории клеточно-молекулярной физиологии и патологии.

Красноярск

Savchenko Andrei Anatyevich - PhD, MD (Medicine), Professor, Head, Laboratory of Molecular and Cellular Physiology and Pathology.

Krasnoyarsk

aasavchenko@yandex.ruБорисовА. Г.BorisovA. G.

Борисов Александр Геннадьевич — кандидат медицинских наук, ведущий научный сотрудник лаборатории клеточно-молекулярной физиологии и патологии.

Красноярск

Borisov Alexandr Gennadyevich - PhD (Medicine), Leading Research Associate, Laboratory of Molecular and Cellular Physiology and Pathology.

Krasnoyarsk

2410454@mail.ruКудрявцевИ. В.KudryavtsevI. V.

Кудрявцев Игорь Владимирович — кандидат биологических наук, старший научный сотрудник отдела иммунологии ИЭМ; доцент кафедры иммунологии Первый Санкт-Петербургский ГМУ им. академика И.П. Павлова.

197376, Санкт-Петербург, ул. Акад. Павлова, 12, Тел.: 8 (812) 234-16-69

Kudryavtsev Igor V. - PhD (Biology), Senior Research Associate, Department of Immunology, IEM; Associate Professor, Department of Immunology, First St.PSI. Pavlov MU.

197376, St. Petersburg, Acad. Pavlov str., 12, Phone: 7(812) 234-16-69

igorek1981@yandex.ruМошевА. В.MoshevA. V.

Мошев Антон Викторович — младший научный сотрудник лаборатории клеточно-молекулярной физиологии и патологии.

Красноярск

Moshev Anton Viktorovich - Junior Research Associate, Laboratory of Molecular and Cellular Physiology and Pathology.

Krasnoyarsk

kinger1@mail2000.ruФГБНУ «Федеральный исследовательский центр „Красноярский научный центр Сибирского отделения Российской академии наук“», обособленное подразделение Научно-исследовательский институт медицинских проблем СевераРоссияResearch Institute of Medical Problems of the North, Krasnoyarsk Science Center, Siberian Branch, Russian Academy of SciencesRussian FederationФРБНУ Институт экспериментальной медицины; ФГБОУВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФРоссияInstitute of Experimental Medicine; First St. Petersburg State I. Pavlov Medical UniversityRussian Federation202014042020222347356Copyright © Савченко А.А., Борисов А.Г., Кудрявцев И.В., Мошев А.В., 20202020Савченко А.А., Борисов А.Г., Кудрявцев И.В., Мошев А.В.Savchenko A.A., Borisov A.G., Kudryavtsev I.V., Moshev 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://www.mimmun.ru/mimmun/article/view/1890

Целью данного исследования явилось изучение зависимости фенотипа и активности респираторного взрыва моноцитов от количества Т-регуляторных клеток (Tregs) у больных с раком почки (РП). Больные с РП (T3N0M0, светлоклеточный тип) были обследованы до хирургического лечения. Фенотип Tregs и моноцитов крови изучали методом проточной цитометрии. Исследование состояния респираторного взрыва моноцитов проводилось путем определения активности люцигенин- и люминол-зависимой спонтанной и зимозан-индуцированной хемилюминесценции. Установлено, что количество Tregs в крови больных с РП было увеличено относительно контрольных значений (у пациентов с РП — Me = 6,3%). Все обследованные пациенты были разделены на две группы в соответствии с медианой по Tregs (менее и более 6,3%). Наиболее выраженные изменения в фенотипе моноцитов и их хемилюминесцентной активности были обнаружены у больных с РП с уровнем Tregs менее 6,3%. Только эта группа пациентов имела перераспределение в субпопуляционном составе моноцитов: уменьшение относительного количества классических моноцитов и увеличение относительного содержания неклассических (провоспалительных) моноцитов. Увеличение абсолютного количества общих моноцитов и уменьшение процентного содержания HLA-DR+ и HLA-DR+CD64+ моноцитов было обнаружено у больных РП независимо от количества Tregs в крови. Изменения в фенотипе моноцитов у больных РП сопровождались изменением состояния их респираторного взрыва. Спонтанный синтез супероксид-радикала (первичная активная форм кислорода — АФК) моноцитами у больных РП с низким уровнем Tregs в крови характеризовался более коротким временем активации НАДФН-оксидазы и более высоким уровнем ее активности, чем у пациентов с высоким содержание Tregs в крови. Индекс активации люцигенин-зависимой хемилюминесценции у больных РП был снижен, не зависел от количества Tregs в крови и определялся, по-видимому, недостаточностью метаболических резервов. Спонтанный синтез вторичных АФК в моноцитах у больных РП был снижен и не зависел от количества Tregs в крови. Индуцированный синтез вторичных АФК и индекс активации их синтеза в моноцитах были снижены только у больных РП с пониженным количеством Tregs в крови. В целом характеристики хемилюминесцентной реакции моноцитов у больных РП определяют наличие дисбаланса между синтезом первичного и вторичного АФК в моноцитах крови. Моноциты у больных РП с низким уровнем Tregs в крови характеризуются большей провоспалительной активностью благодаря быстрой активации и интенсивности синтеза первичных АФК.

The aim of this work was to reveal the interrelations between the number of T regulatory cells (Tregs) in patients with kidney cancer (KC) and phenotype of peripheral blood monocytes and their capacities to produce ROS. Patients with KC (T3N0M0, clear cell type) were examined prior to surgical treatment. Tregs phenotype and blood monocytes were identified by flow cytometry. ROS production of purified monocytes was carried out through the determination of lucigenin- and luminol-dependent spontaneous and zymosan-induced chemiluminescence activity. It has been found that the relative number of Tregs within total lymphocyte subset in KC patients was increased if compared to control values (in KC patients — Me = 6.3%). Then the patients were divided into two groups according to the median of Tregs number (less and more than 6.3%). The most pronounced changes in the phenotype of monocytes and their chemiluminescent activity were found in KC patients with the Tregs count of less than 6.3%. Our findings suggest that low frequency of Tregs in the periphery was associated with increased relative numbers of “intermediate” and “non-classical” (“pro-inflammatory”) monocytes as it was shown on the samples from patients with KC with a low level of Tregs. According to our data, both groups of KC patients had low levels of HLA-DR expression when comparing to control group. Furthermore, both groups of patients had decreased rates of HLA-DR and CD64 co-expressing cells. Changes in the phenotype of monocytes in patients with KC were closely linked with imbalance in ROS production. Thus, the monocytes spontaneous superoxide radical (primary ROS) synthesis in KC patients with a low Treg numbers were characterized by redused NADPH-oxidase activation time and increased level of its activity if compared to patients with a high Treg rates in peripheral blood. Next, the activation index for lucigenin-dependent chemiluminescence in KC patients was reduced, as well as it was independent of circulating Tregs rates and was determined apparently by the insufficiency of metabolic reserves. Similarly, spontaneous secondary ROS production by the monocytes in KC patients was lower then in healthy controls and was also independent of circulating Tregs rates. Finally, the induced secondary ROS synthesis and activation index for their synthesis in monocytes were reduced only in patients with KC with a low number of Tregs in the blood. In general, the characteristics of the chemiluminescent reaction of monocytes in patients with KC determined the imbalance in peripheral blood monocytes primary and secondary ROS production. Monocytes in patients with KC with a low number of Tregs in the blood were characterized by more pro-inflammatory activity due to the rapid activation and intensity of the synthesis of primary ROS.

моноцитырегуляторные Т-лимфоцитырак почкифенотипхемилюминесцентная активностьреспираторный взрывmonocytesTregulatory cellskidney cancerphenotypechemiluminescent activityrespiratory burstДанная работа выполнена при финансовой поддержке Краевого государственного автономного учреждения «Красноярский краевой фонд поддержки научной и научно-технической деятельности» (проект «Механизмы метаболического репрограммирования клеток врожденного иммунитета при опухолевом росте»)The study was performed as part of the project «Mechanisms of metabolic reprogramming of the innate immune cells during tumor growth» was funded by Krasnoyarsk Regional Fund of ScienceReferencesAkinrinmade O.A., Chetty S., Daramola A.K., Islam M.U., Thepen T., Barth S. CD64: an attractive immunotherapeutic target for m1-type macrophage mediated chronic inflammatory diseases. 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The authors declare that there are no conflicts of interest present.