mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-MTM-2141mimmun-2141Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESПротеомное профилирование моноцитоподобных клеток линии THP-1 и продуцируемых ими микровезикул с помощью MALDI-масс-спектрометрииMALDI-TOF mass spectrometric protein profiling of THP-1 cells and their microvesicleshttps://orcid.org/0000-0002-0365-8532КореневскийА. В.KorenevskyA. V.

д.б.н., ведущий научный сотрудник, руководитель группы протеомной иммунорегуляции отдела иммунологии и межклеточных взаимодействий,

199034, Санкт-Петербург, Менделеевская линия, 3

PhD, MD (Biology), Leading Research Associate, Head, Proteomic Immunoregulation Group, Department of Immunology and Cell Interactions, 

St. Petersburg

a.korenevsky@yandex.ruhttps://orcid.org/0000-0003-1951-8312МилютинаЮ. П.MilyutinaYu. P.

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

Санкт-Петербург

PhD (Biology), Senior Research Associate, Proteomic Immunoregulation Group, Department of Immunology and Cell Interactions, 

St. Petersburg

milyutina1010@mail.ruhttps://orcid.org/0000-0002-9677-8479БерезкинаМ. Э.BerezkinaM. E.

лаборант-исследователь лаборатории межклеточных взаимодействий отдела иммунологии и межклеточных взаимодействий,

Санкт-Петербург

Research Assistant, Laboratory of Cell Interactions, Department of Immunology and Cell Interactions,

St. Petersburg

mari-xari@list.ruАлександровнаЕ. П.AlexandrovaE. P.

 студент лаборатории межклеточных взаимодействий отдела иммунологии и межклеточных взаимодействий,

Санкт-Петербург

Student, Laboratory of Cell Interactions, Department of Immunology and Cell Interactions, 

St. Petersburg

alyx-katich@mail.ruБалабасО. А.BalabasO. A.

ведущий специалист ресурсного центра «Методы анализа состава вещества»,

Санкт-Петербург

Leading Specialist, Chemical Analysis and Materials Research Centre, 

St. Petersburg

o.balabas@spbu.ruhttps://orcid.org/0000-0003-2748-3543МарковаК. Л.MarkovaK. L.

младший научный сотрудник лаборатории межклеточных взаимодействий отдела иммунологии и межклеточных взаимодействий,

Санкт-Петербург

Junior Research Associate, Laboratory of Cell Interactions, Department of Immunology and Cell Interactions,

St. Petersburg

kseniyabelyakova129@gmail.comhttps://orcid.org/0000-0003-1560-7529СельковС. А.SelkovS. A.

д.м.н., профессор, заслуженный деятель науки РФ, руководитель отдела иммунологии и межклеточных взаимодействий,

Санкт-Петербург

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

St. Petersburg

selkovsa@mail.ruhttps://orcid.org/0000-0002-5749-2531СоколовД. И.SokolovD. I.

д.б.н., доцент, заведующий лабораторией межклеточных взаимодействий Отдела иммунологии и межклеточных взаимодействий,

Санкт-Петербург

PhD, MD (Biology), Head, Laboratory of Cell Interactions, Department of Immunology and Cell Interactions,

St. Petersburg

falcojugger@yandex.ruФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»РоссияD. Ott Institute of Obstetrics, Gynecology and ReproductologyRussian FederationФГБОУ ВО «Санкт-Петербургский государственный университет»РоссияSt. Petersburg State UniversityRussian FederationФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии им. Д.О. Отта»РоссияD. Ott Institute of Obstetrics, Gynecology and ReproductologyRussian Federation202124042021232275292Copyright © Кореневский А.В., Милютина Ю.П., Березкина М.Э., Александровна Е.П., Балабас О.А., Маркова К.Л., Сельков С.А., Соколов Д.И., 20212021Кореневский А.В., Милютина Ю.П., Березкина М.Э., Александровна Е.П., Балабас О.А., Маркова К.Л., Сельков С.А., Соколов Д.И.Korenevsky A.V., Milyutina Y.P., Berezkina M.E., Alexandrova E.P., Balabas O.A., Markova K.L., Selkov S.A., Sokolov D.I.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/2141

Отделяющиеся от плазматической мембраны клетки экстраклеточные везикулы принимают активное участие в межклеточной коммуникации, транспортируя широкий спектр молекул, среди которых важное функциональное значение придается белкам, липидам, нуклеиновым кислотам и сахарам. Одним из важных этапов в понимании дистантной коммуникации клеток и механизмов ее регуляции является изучение протеома различных экстраклеточных везикул, в том числе микровезикул и экзосом. Синтезируемые моноцитами провоспалительные цитокины и отдельные компоненты системы комплемента играют ключевую роль в осуществлении их специфических функций. Целью данного исследования явилось изучение протеомного состава моноцитоподобных клеток линии THP-1 и продуцируемых ими микровезикул. В результате MALDI-масс-спектрометрического анализа электрофоретических белковых фракций лизата клеток и микровезикул идентифицировано 107 белков, выполняющих различные функции. Среди 19 функциональных групп наибольшие по численности группы образуют белки-регуляторы транскрипции и белки c неизвестными функциями, домены. Наименьшие по численности функциональные группы представлены белками-регуляторами клеточной дифференцировки и морфогенеза, белками иммунного ответа и воспаления, рецепторами и их регуляторами, транспортными белками и белками-регуляторами транспорта, белками-регуляторами клеточной адгезии и процессинга белков, белками убиквитин-протеасомной системы деградации белков, белками внутриклеточной сигнализации, белками-регуляторами аутофагоцитоза и экзоцитоза, белками структуры хроматина, белками-регуляторами гемостаза, гормонами. Промежуточное положение занимают цитокины и факторы роста, ферменты, белки цитоскелета, структурные и моторные белки, белки-регуляторы трансляции, транскрипции и процессинга РНК. С помощью последующего кластерного анализа (DAVID Functional Annotation Clustering) идентифицированы наиболее широко представленные группы белков, распределенных по молекулярной функции, биологическому процессу и по положению в клетке. Отдельно в микровезикулах идентифицированы среди прочих белковых молекул белки иммунного ответа и воспаления, цитокины и факторы роста, белки внутриклеточной сигнализации, белки-регуляторы клеточной дифференцировки и морфогенеза, белки-регуляторы клеточной адгезии. Полученные данные о частичном протеоме моноцитоподобных клеток линии THP-1 и продуцируемых ими микровезикул расширяют имеющиеся представления о дистантной коммуникации клеток и указывают на новые механизмы взаимодействия моноцитов/макрофагов и их микроокружения. 

Extracellular vesicles that are shed from the plasma membranes take an active part in intercellular communication, transporting a wide range of molecules, including proteins, lipids, nucleic acids and carbohydrates, being of great functional importance. One of the steps to better understanding of distant communications of cells and their regulatory mechanisms is a proteomic study of various extracellular vesicles, including microvesicles and exosomes. Pro-inflammatory cytokines produced by monocytes and individual complement system components play a key role in their specific functioning. The aim of this work was to study proteomic composition of THP-1 monocyte-like cells and their microvesicles. The MALDI-mass spectrometric analysis of electrophoretic protein fractions of cell lysates and microvesicles allowed for identifying 107 proteins that perform various functions. Among 19 determined functional groups, the largest ones comprise transcription regulators and proteins with unknown functions. The smallest functional groups include regulators of cell differentiation and development, proteins participating in immune response and inflammation, cellular receptors and their regulators, transporter and transport regulatory proteins, as well as cell proteins mediating adhesion and matrix structures, processing regulators, proteins of ubiquitin-proteasome system, intracellular signaling, autophagy and exocytosis regulators, chromatin structural proteins, hemostatic regulators, and peptide hormones. An intermediate position is occupied by cytokines and growth factors, enzymes, cytoskeleton and motor proteins, as well as RNA processing and translation regulators. The subsequent DAVID Functional Annotation Clustering analysis allowed for identifying the most common groups distributed by their molecular function, biological processes, and cellular component. Separately, in the microvesicles derived from THP-1 monocyte-like cells, proteins of the immune response and inflammation, cytokines and growth factors, intracellular signaling proteins, cell differentiation regulators and developmental proteins, as well as cell adhesion and matrix proteins were identified among other protein molecules. The data obtained on the partial proteome of THP-1 monocyte-like cells and their microvesicles extend the existing knowledge on distant communications between the cells and suggest new mechanisms of interaction between monocytes/macrophages and their microenvironment. 

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