mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-PLI-2511mimmun-2511Research ArticleОБЗОРЫREVIEWSТромбоцитарно-лейкоцитарные взаимодействия: иммунорегуляторная роль и патофизиологическое значениеPlatelet-leukocyte interactions: immunoregulatory role and pathophysiological relevancehttps://orcid.org/0000-0003-4873-4081ПавловО. В.PavlovO. V.

Павлов Олег Владимирович, д.б.н., ведущий научный сотрудник отдела иммунологии и межклеточных взаимодействий

199034, Санкт-Петербург, Менделеевская линия, 3Teл.: 8 (812) 328-98-50Факс: 8 (812) 323-75-45

Pavlov Oleg V. PhD, MD (Biology), Leading Research Associate, Department of Immunology and Cell Interaction

199034, St. Petersburg, Mendeleevskaya Line, 3Phone: 7 (812) 328-98-50Fax: 7 (812) 323-75-45

ovpavlov@hotmail.comЧепановС. В.ChepanovS. V.

к.м.н., старший научный сотрудник отдела иммунологии и межклеточных взаимодействий

Санкт-Петербург

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

St. Petersburg

chepanovsv@gmail.comСелютинА. В.SelutinA. V.

к.б.н., старший научный сотрудник отдела иммунологии и межклеточных взаимодействий

Санкт-Петербург

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

St. Petersburg

a_selutin@yahoo.comhttps://orcid.org/0000-0003-1560-7529СельковС. А.SelkovS. A.

д.м.н., профессор, заслуженный деятель науки РФ, заведующий отделом иммунологии и межклеточных взаимодействий; профессор кафедры иммунологии

Санкт-Петербург

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

St. Petersburg

selkovsa@mail.ruФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»РоссияD. Ott Institute of Obstetrics, Gynecology, and Reproductive MedicineRussian FederationФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»; ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФРоссияD. Ott Institute of Obstetrics, Gynecology, and Reproductive Medicine; First St. Petersburg State I. Pavlov Medical UniversityRussian Federation202231102022245871888Copyright © Павлов О.В., Чепанов С.В., Селютин А.В., Сельков С.А., 20222022Павлов О.В., Чепанов С.В., Селютин А.В., Сельков С.А.Pavlov O.V., Chepanov S.V., Selutin A.V., Selkov S.A.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/2511

Тромбоциты не только являются важнейшими участниками процессов тромбообразования и свертывания крови, но и обладают иммунорегуляторными свойствами, представляя собой связующее звено между системой гемостаза и иммунной системой. Морфофункциональные характеристики тромбоцитов обеспечивают постоянное мониторирование состояния кровеносной системы, выявление угроз различного характера, формирование ответа и вовлечение в него в том числе иммунокомпетентных клеток. Дистантные межклеточные взаимодействия тромбоцитов с лейкоцитами осуществляются посредством иммунорегуляторных молекул, которые наряду с факторами коагуляции и тромбообразования выделяются в результате активации и дегрануляции тромбоцитов. Продуцируемые активированными тромбоцитами хемокины, цитокины, ростовые факторы, некоторые из которых синтезируются de novo, оказывают модулирующее действие на функции клеток врожденного и адаптивного звена иммунной системы. Активированные тромбоциты вступают в непосредственный контакт с иммунокомпетентными клетками, в результате чего формируются гетеротипические агрегаты – тромбоцитарно-лейкоцитарные комплексы, – которые наряду с форменными элементами крови циркулируют в кровеносной системе. Образование и стабилизация агрегатов осуществляются за счет взаимодействия различных молекул, экспрессируемых на поверхности тромбоцитов и лейкоцитов, главную роль среди которых играет пара P-селектин (CD62P) – PSGL-1 (CD162). Наиболее многочисленными являются комплексы тромбоцитов с моноцитами и нейтрофилами, при этом тромбоцитарно-моноцитарные комплексы отличаются наибольшей стабильностью. Микровезикулы тромбоцитарного происхождения также вступают во взаимодействие с лейкоцитами с образованием гетеротипических агрегатов и предположительно оказывают модулирующее воздействие на функции иммунных клеток посредством переноса некодирующих молекул РНК. Формирование тромбоцитарно-лейкоцитарных комплексов приводит к взаимной активации тромбоцитов и лейкоцитов. Под действием тромбоцитов и тромбоцитарных микровезикул в моноцитах и нейтрофилах происходит усиление секреции цитокинов и реактивных форм кислорода, фагоцитарной активности, индуцируется образование нейтрофильной внеклеточной ловушки и прокоагулянтный фенотип моноцитов. Тромбоциты оказывают регуляторное влияние на дифференцировку моноцитов, усиливают адгезию и трансмиграцию лимфоцитов и NK-клеток. В очагах воспаления тромбоциты способствуют экстравазации и инфильтрации лейкоцитов в поврежденные участки тканей. Нарушения во взаимодействии тромбоцитов с клетками эндотелия сосудов и клетками иммунной системы могут лежать в основе различных патологических состояний. Повышенный уровень циркулирующих тромбоцитарно-лейкоцитарных комплексов наблюдается при многих патологических состояниях, в числе которых сердечно-сосудистые и респираторно-легочные заболевания, заболевания почек, заболевания печени, сахарный диабет, репродуктивные патологии, бактериальные и вирусные инфекции. Изучение тромбоцитарно-лейкоцитарных взаимодействий необходимо для уточнения патогенеза и выработки новых терапевтических подходов к лечению этих заболеваний.

Blood platelets are the central players in thrombosis and blood coagulation. Moreover, they also exhibit immunoregulatory properties and bridge hemostasis and immunity. Morphological and functional characteristics of the platelets ensure continuous surveillance for the vascular system, recognition of different hazards, development of appropriate response and recruitment of immune cells. Indirect platelet-leukocyte interactions are mediated by immunoregulatory molecules that are released, along with coagulation and thrombosis factors in the course of platelet activation and degranulation. Chemokines, cytokines, growth factors, some of which are synthesized de novo, are released from activated platelets and modulate cellular functions, thus modulating both innate and adaptive immune response. Activated platelets enter contacts with immune cells to form heterotypic aggregates, i.e., platelet-leukocyte complexes that reside in blood circulation along with other blood cells. The aggregate formation and stabilization is mediated by interaction between the molecules expressed on the surface of platelets and leukocytes, in particular, P-selectin (CD62P) and PSGL-1 (CD162). Platelet-monocyte and platelet-neutrophil complexes are most abundant, with platelet-monocyte aggregates being most stable. Moreover, the platelet-derived microvesicles also interact with leukocytes to form heterotypic aggregates, thus, probably, modulating the immune cell functions via transfer of non-coding RNA molecules. Formation of platelet-leukocyte complexes results into mutual activation of platelets and leukocytes. Platelets and platelet-derived microvesicles stimulate phagocytic activity, cytokine secretion, and generation of reactive oxygen species in monocytes and neutrophils, inducing formation of neutrophilic extracellular traps and procoagulant phenotype in monocytes. The blood platelets regulate monocyte differentiation, promote adhesion, as well as transmigration of lymphocytes and NK cells. At the sites of inflammation, platelets enhance extravasation and infiltration of leukocytes into the damaged tissue. Impaired interactions of platelets with endothelial layer and immune cells may underlie pathogenic conditions. Increased level of circulating plateletleukocyte complexes is observed in various disorders including cardiovascular diseases, acute ischemic stroke, respiratory disorders, renal pathologies, liver diseases, diabetes, reproductive disorders, bacterial and viral infections. Further studies of platelet-leukocyte interactions are warranted to unveil pathogenic mechanisms and to develop new therapeutic approaches.

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