mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-PCA-2941mimmun-2941Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESТРОМБОЦИТАРНО-МОНОЦИТАРНЫЕ КОМПЛЕКСЫ И ИХ ВОЗМОЖНАЯ РОЛЬ В ПАТОГЕНЕЗЕ ПРЕЭКЛАМПСИИPLATELET-MONOCYTE COMPLEXES AND THEIR POTENTIAL ROLE IN THE PATHOGENESIS OF PREECLAMPSIAhttps://orcid.org/0000-0003-4873-4081ПавловОлег ВладимировичPavlovOleg

доктор биологических наук, старший научный сотрудник отдела иммунологии и межклеточных взаимодействий

PhD, MD (Biology), Senior Research Associate, Department of Immunology and Cell Interaction

ovpavlov@hotmail.comЧепановСергей ВладимировичChepanovSergei

кандидат медицинских наук, старший научный сотрудник отдела иммунологии и межклеточных взаимодействий 

PhD (Medicine), Senior Research Associate, Department of Immunology and Cell Interaction

chepanovsv@gmail.comПеретятькоИлья СергеевичPeretyatkoIlya

врач акушер-гинеколог родильного отделения 

obstetrician-gynecologist, Maternity Department

doc.pere@yandex.ruМозговаяЕлена ВитальевнаMozgovayaElena

доктор медицинских наук, ведущий научный сотрудник отдела акушерства и перинатологии 

PhD, MD (Medicine), Leading Research Associate, Department of Obstetrics and Perinatology

Elmozg@mail.ruКоганИгорь ЮрьевичKoganIgor

доктор медицинских наук, чл.-корр. РАН, профессор, директор ФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»

PhD, MD (Medicine), corresponding member Russian Academy of Sciences, Professor, Director, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductive Medicine

ncotta@mail.ruhttps://orcid.org/0000-0003-1560-7529СельковСергей АлексеевичSelkovSergei

доктор медицинских наук, профессор, заслуженный деятель науки РФ, заведующий отделом иммунологии и межклеточных взаимодействий

PhD, MD (Medicine), Professor, Honored Scientist of the Russian Federation, Head, Department of Immunology and Cell Interaction

selkovsa@mail.ruФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»РоссияD.O. Ott Research Institute of Obstetrics, Gynecology and Reproductive MedicineRussian Federation20192006202400Online First2941Copyright © Павлов О.В., Чепанов С.В., Перетятько И.С., Мозговая Е.В., Коган И.Ю., Сельков С.А., 20192019Павлов О.В., Чепанов С.В., Перетятько И.С., Мозговая Е.В., Коган И.Ю., Сельков С.А.Pavlov O., Chepanov S., Peretyatko I., Mozgovaya E., Kogan I., Selkov S.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2941

Резюме. Беременность характеризуется особым состоянием системы гемостаза и иммунной системы, при котором наблюдается активация их компонентов. Гиперактивация тромбоцитов и моноцитов может являться фактором, вызывающим различные осложнения беременности, в частности, преэклампсию. При этом патогенетическая роль тромбоцитарно-моноцитарных комплексов (ТМК), которые представляют интерес в качестве диагностического маркера и в качестве терапевтической мишени, исследована недостаточно. Целью исследования было определение количественных изменений в содержании и фенотипических характеристиках ТМК периферической крови при преэклампсии, а также оценка влияния тромбоцитов на экспрессию поверхностных маркерных белков моноцитов при физиологическом и патологическом течении беременности. Исследуемые группы составили женщины в возрасте 24-42 года с диагнозом тяжелая преэклампсия (35-41 недель беременности) и женщины с неосложненной (физиологической) беременностью  (33-41 недель беременности). В общей популяции и субпопуляциях моноцитов периферической крови пациенток методами проточной цитофлориметрии определяли содержание ТМК и уровни экспрессии CD62P, CD11b, CD86, CD162, HLA-DR, TREM-1 как в составе комплексов, так и в свободно циркулирующих клетках. Установлено, что при преэклампсии уровень ТМК повышен (29,3% всей популяции моноцитов) в сравнении с беременностью, протекающей без осложнений (17,5%), и это повышение происходит за счет двух субпопуляций моноцитов, их формирующих: классических и промежуточных. При этом в ТМК отмечено повышение уровней экспрессии поверхностных антигенов CD62P, CD162, HLA-DR, CD86, TREM-1, CD11b характеризующих  активацию тромбоцитов и моноцитов. Фракции классических, промежуточных и неклассических моноцитов вносили различный вклад в изменение уровней экспрессии активационных маркеров моноцитов, связанное с преэклампсией. Сравнение ТМК и свободно циркулирующих моноцитов показало, что изменения поверхностного антигенного фенотипа моноцитов в составе ТМК обусловлены как влиянием тромбоцитов, так и другими факторами. При  преэклампсии наблюдается индуцированное тромбоцитами усиление провоспалительных и адгезионных свойств моноцитов, что проявляется  в повышение уровней экспрессии TREM-1 и CD11b в ТМК. В то же время повышение уровней экспрессии HLA-DR и CD86 в моноцитах не связано с их взаимодействием с тромбоцитами. Полученные результаты свидетельствуют о том, что преэклампсия сопровождается повышением содержания ТМК в периферической крови и активацией моноцитов в составе ТМК,  демонстрируют иммуномодуляторное влияние тромбоцитов, а также дают обоснования значимости определения паттернов экспрессии поверхностных антигенных маркеров ТМК в диагностических и терапевтических целях.

Abstract. Pregnancy represents the state with particularly activated constituents of hemostasis and immune systems. Hyperactivation of platelets and monocytes may be a causative factor for pregnancy complications including preeclampsia. The pathogenetic role of platelet-monocyte complexes (PMC), recognized as diagnostic marker and therapeutic target, is poorly investigated. The aim of the study was to determine quantitative changes in the peripheral blood PMC level and antigenic phenotype in preeclampsia, and to evaluate effects of platelets on the expression of monocyte surface marker proteins in normal and pathological pregnancy. The tested groups included third trimester pregnant women diagnosed with severe preeclampsia (35-41 weeks of gestation) and women with uncomplicated (physiological) pregnancies (33-41 weeks of gestation). All participants were between the age of 24 and 42 years. PMC levels and CD62P, CD11b, CD86, CD162, HLA-DR, TREM-1 expressed by PMC and free circulating cells were determined by flow cytometry in the peripheral blood total monocytes and monocyte subpopulations.It was found that PMC level increased (29.2% of total monocyte population) when compared to uncomplicated pregnancy (17.5%), and this augmentation was ensured by two PMC-forming monocyte subpopulations: classical and intermediate. Moreover, expression levels of platelet and monocyte activation markers CD62P, CD162, HLA-DR, CD86, TREM-1, CD11b were significantly higher in preeclampsia. The fractions of classical, intermediate and non-classical monocytes differently contributed to preeclampsia-associated changes in the expression levels of monocyte activation markers. Comparison of PMC and free circulating monocytes demonstrated that observed changes in the surface antigenic phenotype of monocytes within PMC were ensured by platelets and other factors. In preeclampsia, platelet-induced augmentation of monocyte inflammatory and adhesive capacities displayed itself in the increased TREM-1 and CD11b expression. In contrast, increased levels of HLA-DR and CD86 in monocytes were not induced by the interaction with platelets. The results of the study suggest that preeclampsia is accompanied by increased peripheral blood PMC levels and activation of monocytes within PMC, demonstrate immunomodulatory effect of platelets, and provide a rationale for the evaluation of expression patterns of PMC surface antigenic markers with diagnostic and therapeutic purposes.

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