mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-MMS-1976mimmun-1976Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESПротеомное профилирование микровезикул клеток естественных киллеров линии NK-92 с помощью MALDI-масс-спектрометрииMALDI-TOF mass spectrometric protein profiling of microvesicles produced by the NK-92 natural killer cell linehttps://orcid.org/0000-0002-0365-8532КореневскийА. В.KorenevskyA. V.

Кореневский Андрей Валентинович – доктор биологических наук, ведущий научный сотрудник, руководитель группы протеомной иммунорегуляции отдела иммунологии  и межклеточных  взаимодействий.

199034, Санкт-Петербург, Менделеевская линия, 3, Тел.: 8 (812) 328-98-91, 323-75-45,  Факс: 8 (812) 323-75-45

Korenevsky Andrey Valentinovich - PhD, MD (Biology), Leading Research Associate, Proteomic Immunoregulation  Group, Department of Immunology and Cell Interactions.

199034, St. Petersburg, Mendeleyevskaya line, 3, Phone: 7 (812) 328-98-91, 323-75-45. Fax: 7 (812) 323-75-45

a.korenevsky@yandex.ruЩербицкаяА. Д.ShcherbitskaiaA. D.

Щербицкая Анастасия Дмитриевна – кандидат биологических наук,  научный сотрудник лаборатории сравнительной  физиологии и патологии.

Санкт-Петербург

Shcherbitskaya Anastasiia Dmitrievna - PhD (Biology), Research Associate, Laboratory of Comparative Physiology and Pathology of the Central Nervous System.

St. Petersburg

nastusiq@gmail.comБерезкинаМ. Э.BerezkinaM. E.

Березкина Марьяна Эдуардовна  – лаборант-исследователь лаборатории межклеточных  взаимодействий отдела иммунологии  и межклеточных  взаимодействий.

Санкт-Петербург

Berezkina Maryana Eduardivna - Research Assistant, Laboratory of Cell Interactions, Department of Immunology and Cell Interactions.

mari-xari@list.ruМарковаК. Л.MarkovaK. L.

Маркова Ксения Львовна – младший научный сотрудник лаборатории межклеточных  взаимодействий отдела иммунологии  и межклеточных  взаимодействий.

Markova Kseniya Lvovna -  Junior Research Associate, Laboratory of Cell Interactions, Department of Immunology and Cell Interactions.

kseniyabelyakova129@gmail.comАлександроваЕ. П.AlexandrovaE. P.

Александрова                 Екатерина Павловна – лаборант-исследователь лаборатории межклеточных  взаимодействий отдела иммунологии  и межклеточных  взаимодействий НИИАГР им. Д.О. Отта.

Alexandrova Ekaterina Pavlovna - Research Assistant, Laboratory of Cell Interactions, Department of Immunology and Cell Interactions.

St. Petersburg

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

Балабас Ольга Алексеевна  – ведущий специалист.

Balabas Olga Alexeyevna - Leading Specialist, Chemical Analysis and Materials Research Centre.

o.balabas@spbu.ruhttps://orcid.org/0000-0003-1560-7529СельковС. А.SelkovS. A.

Сельков Сергей Алексеевич – доктор медицинских наук, профессор, руководитель отдела иммунологии  и межклеточных  взаимодействий НИИАГР имени Д.О. Отта»; профессор кафедры иммунологии  Первый С-ПГМУ им. Академика.

Санкт-Петербург

Selkov Sergey Alexeyevich - PhD, MD (Medicine), Professor, Head, Department of Immunology and Cell Interactions, D. Ott RIO, GR; Professor, Department of Immunology, First St. Petersburg State I. Pavlov MU.

St. Petersburg

selkovsa@mail.ruСоколовД. И.SokolovD. I.

Соколов Дмитрий Игоревич – доктор биологических наук, доцент, заведующий лабораторией межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий НИИАГР имени Д.О. Отта»; доцент кафедры иммунологии Первый С-ПГМУ им. академика И.П. Павлова.Санкт-Петербург

Sokolov Dmitry Igorevich - PhD, MD (Biology), Associate Professor, Head, Cell Interactions Laboratory, Department of Immunology and Cell Interactions, D. Ott RIO, GR; Associate Professor, Department of Immunology, First St. Petersburg State I. Pavlov MU.

falcojugger@yandex.ruФГБНУ Научно-исследовательский институт акушерства, гинекологии и репродуктологии им. Д.О. ОттаРоссияD.O. Ott Research Institute of Obstetrics, Ginecology, and ReproductologyRussian FederationФГБУН Институт эволюционной физиологии и биохимии имени И.М. Сеченова, Российская академия наукРоссияI. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of SciencesRussian FederationФГБНУ Научно-исследовательский институт акушерства, гинекологии и репродуктологии им. Д.О. ОттаРоссияD. Ott Research Institute of Obstetrics, Gynecology, and ReproductologyRussian FederationРесурсный центр Методы анализа состава вещества, ФГБОУ ВО Санкт-Петербургский государственный университетРоссияChemical Analysis and Materials Research Centre, St. Petersburg State UniversityRussian 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 РФРоссия.D. Ott Research Institute of Obstetrics, Gynecology, and Reproductology; First St. Petersburg State I. Pavlov Medical UniversityRussian 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 Research Institute of Obstetrics, Gynecology, and Reproductology; First St. Petersburg State I. Pavlov Medical UniversityRussian Federation202003082020224633646Copyright © Кореневский А.В., Щербицкая А.Д., Березкина М.Э., Маркова К.Л., Александрова Е.П., Балабас О.А., Сельков С.А., Соколов Д.И., 20202020Кореневский А.В., Щербицкая А.Д., Березкина М.Э., Маркова К.Л., Александрова Е.П., Балабас О.А., Сельков С.А., Соколов Д.И.Korenevsky A.V., Shcherbitskaia A.D., Berezkina M.E., Markova K.L., Alexandrova E.P., Balabas O.A., 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/1976

Отделяющиеся от плазматической мембраны клетки экстраклеточные везикулы служат транспортерами широкого спектра молекул, среди  которых важное функциональное значение придается  белкам, липидам, нуклеиновым кислотам и сахарам. Цитотоксические белки  естественных киллеров играют  ключевую роль  в осуществлении их цитолитических функций. Одним из важных этапов в понимании дистантной коммуникации клеток и механизмов ее регуляции является определение протеомного состава микровезикул. Целью данного исследования явилось изучение протеомного состава микровезикул, образуемых клетками естественных киллеров линии NK-92. В результате MALDI-TOF-масс-спектрометрического анализа белковых фракций лизата  микровезикул было идентифицировано 986 белков, выполняющих различные функции. С помощью автоматизированных  методов функционального анализа показано, что  наибольшие по  численности группы белков представляют гипотетические белки, белки  c неизвестными функциями, домены. Наиболее представительные группы также образуют регуляторы транскрипции, белки  внутриклеточной сигнализации, регуляторы трансляции,  транскрипции,  процессинга и  утилизации РНК,  рецепторы, регуляторы процессинга и протеолиза белков, ферменты обмена аминокислот, а также  транспортные белки  и регуляторы транспорта. Минорные функциональные группы представлены ферментами обмена витаминов и минерального обмена, мембранными и микродоменобразующими белками, гормонами, регуляторами гемостаза, сенсорных систем, специфическими митохондриальными белками и белками аппарата Гольджи, белками межклеточной сигнализации. Промежуточное положение занимают различные функциональные группы, в том числе  белки  цитоскелета, структурные и моторные белки, белки  центриолей, ионные каналы и их регуляторы, белки  убиквитин-протеасомной системы деградации белков, ферменты обмена липидов, стероидов и жирных кислот, нуклеиновых (азотистых) оснований, углеводов, а также  ферменты энергетического обмена и другие белки-участники промежуточного метаболизма, белки  иммунного ответа  и воспаления, антигены и белки  гистосовместимости, цитокины и факторы роста, регуляторы апоптоза, аутофагоцитоза, эндоцитоза и экзоцитоза, регуляторы клеточного цикла и деления, регуляторы пролиферации, клеточной дифференцировки и морфогенеза, регуляторы клеточной адгезии, метаболизма матрикса и адгезии к нему, ядерные транспортные белки, белки  транспозиции, белки  систем репликации и репарации ДНК, а также  неактивные белки. Полученные данные расширяют имеющиеся представления о дистантной коммуникации клеток и указывают на новые механизмы взаимодействия естественных киллеров и клеток-мишеней.

Extracellular vesicles that are shed from the plasma membrane contain a wide range of molecules, among  which  are proteins, lipids, nucleic  acids,  and sugars. The cytotoxic proteins of natural killer cells play a key role in the implementation of their cytolytic  functions. One of the important steps in understanding the distant  communication of cells is the determination of the proteome of microvesicles. This study was aimed at the protein profiling of the microvesicles produced by the NK-92 natural killer cell line. 986 proteins with a variety of functions were identified in the lysate of microvesicles using the MALDI-TOF mass spectrometric analysis.  With automated methods of functional analysis  applied, it has been  shown  that  the  largest  protein groups  are  hypothetical proteins, proteins with  unknown functions, and  domains. The  most  representative groups  are  also  comprised by  transcription  regulators; intracellular  signaling  proteins; RNA  translation, transcription, processing, and utilization regulators; receptors; protein processing  and proteolysis regulators; amino acid metabolism enzymes, as well as transport proteins and transport regulators. Minor functional groups are represented by vitamins and mineral metabolism enzymes, membrane and microdomain-forming proteins, hormones, hemostatic regulators, regulators of sensory  systems,  specific  mitochondrial and  Golgi  apparatus proteins, and extracellular signaling proteins. An intermediate position is occupied by various functional groups, including cytoskeleton and motor proteins; proteins of centrioles; ion channels and their regulators; proteins of the ubiquitin-proteasome pathway  of protein degradation; lipid,  steroid, and fatty acid metabolism enzymes; nucleic  acid  base and  carbohydrate metabolism enzymes, as well as energy  metabolism enzymes  and  other proteins involved  in intermediate metabolism; proteins of the immune response  and  inflammation; antigens and histocompatibility proteins; cytokines and growth factors; regulators of apoptosis, autophagy, endocytosis, and  exocytosis;  regulators of the  cell cycle and  division;  regulators of proliferation, cell differentiation, and morphogenesis; regulators of cell adhesion and  matrix  metabolism; nuclear transport proteins; transposition proteins; DNA  replication and  repair  proteins, as well as inactive  proteins. The  data  obtained expand  the existing knowledge of the distant  communication of cells and indicate new mechanisms of interaction between natural killer and target cells.

естественные киллерымикровезикулыиммунный ответвоспалениепротеомMALDI-TOF-массспектрометрияnatural killer cellsmicrovesiclesimmune responseinflammationproteomeMALDI-TOF mass spectrometryРоссийский фонд фундаментальных исследований, НИИ акушерства, гинекологии и репродуктологии им. Д.О. ОттаThis work was supported by the Russian Foundation for Basic Research (Project Registration No. 19-015-00218) and was performed in the Department of Immunology and Cell Interactions, D. Ott Institute of Obstetrics, Gynecology, and Reproductology (St. Petersburg, Russia), partially within the institutional state assignment framework (R&D State Registration No. AAAA-A19-119021290116-1), using the equipment of Chemical Analysis and Materials Research Centre, St. Petersburg State University (St. Petersburg, Russia)ReferencesBrittoli A., Fallarini S., Zhang H., Pieters R.J., Lombardi G. “In vitro” studies on galectin-3 in human natural killer cells. Immunol. Lett., 2018, Vol. 194, pp. 4-12.Brittoli A., Fallarini S., Zhang H., Pieters R.J., Lombardi G. “In vitro” studies on galectin-3 in human natural killer cells. Immunol. Lett., 2018, Vol. 194, pp. 4-12.Burbano C., Rojas M., Vasquez G., Castano D. Microparticles that form immune complexes as modulatory structures in autoimmune responses. Mediators Inflamm., 2015, Vol. 2015, 267590. doi: 10.1155/2015/267590.Burbano C., Rojas M., Vasquez G., Castano D. Microparticles that form immune complexes as modulatory structures in autoimmune responses. Mediators Inflamm., 2015, Vol. 2015, 267590. doi: 10.1155/2015/267590.Cepero-Donates Y., Rakotoarivelo V., Mayhue M., Ma A., Chen Y.G., Ramanathan S. Homeostasis of IL-15 dependent lymphocyte subsets in the liver. Cytokine, 2016, Vol. 82, pp. 95-101.Cepero-Donates Y., Rakotoarivelo V., Mayhue M., Ma A., Chen Y.G., Ramanathan S. Homeostasis of IL-15 dependent lymphocyte subsets in the liver. Cytokine, 2016, Vol. 82, pp. 95-101.Haraszti R.A., Didiot M.C., Sapp E., Leszyk J., Shaffer S.A., Rockwell H.E., Gao F., Narain N.R., DiFiglia M., Kiebish M.A., Aronin N., Khvorova A. High-resolution proteomic and lipidomic analysis of exosomes and microvesicles from different cell sources. J. Extracell. Vesicles, 2016, Vol. 5, no. 1, 32570. doi: 10.3402/jev.v5.32570.Haraszti R.A., Didiot M.C., Sapp E., Leszyk J., Shaffer S.A., Rockwell H.E., Gao F., Narain N.R., DiFiglia M., Kiebish M.A., Aronin N., Khvorova A. High-resolution proteomic and lipidomic analysis of exosomes and microvesicles from different cell sources. J. Extracell. Vesicles, 2016, Vol. 5, no. 1, 32570. doi: 10.3402/jev.v5.32570.Holt D., Ma X., Kundu N., Fulton A. Prostaglandin E(2) (PGE (2)) suppresses natural killer cell function primarily through the PGE(2) receptor EP4. Cancer Immunol. Immunother., 2011, Vol. 60, no. 11, pp. 1577-1586.Holt D., Ma X., Kundu N., Fulton A. Prostaglandin E(2) (PGE (2)) suppresses natural killer cell function primarily through the PGE(2) receptor EP4. Cancer Immunol. Immunother., 2011, Vol. 60, no. 11, pp. 1577-1586.Honorati M.C., Neri S., Cattini L., Facchini A. IL-17 enhances the susceptibility of U-2 OS osteosarcoma cells to NK cell lysis. Clin. Exp. Immunol., 2003, Vol. 133, no. 3, pp. 344-349.Honorati M.C., Neri S., Cattini L., Facchini A. IL-17 enhances the susceptibility of U-2 OS osteosarcoma cells to NK cell lysis. Clin. Exp. Immunol., 2003, Vol. 133, no. 3, pp. 344-349.Jaime P., Garcia-Guerrero N., Estella R., Pardo J., Garcia-Alvarez F., Martinez-Lostao L. CD56(+)/CD16(-) Natural killer cells expressing the inflammatory protease granzyme A are enriched in synovial fluid from patients with osteoarthritis. Osteoarthritis Cartilage, 2017, Vol. 25, no. 10, pp. 1708-1718.Jaime P., Garcia-Guerrero N., Estella R., Pardo J., Garcia-Alvarez F., Martinez-Lostao L. CD56(+)/CD16(-) Natural killer cells expressing the inflammatory protease granzyme A are enriched in synovial fluid from patients with osteoarthritis. Osteoarthritis Cartilage, 2017, Vol. 25, no. 10, pp. 1708-1718.Jong A.Y., Wu C.H., Li J., Sun J., Fabbri M., Wayne A.S., Seeger R.C. Large-scale isolation and cytotoxicity of extracellular vesicles derived from activated human natural killer cells. J. Extracell. Vesicles, 2017, Vol. 6, no. 1, 1294368. doi: 10.1080/20013078.2017.1294368.Jong A.Y., Wu C.H., Li J., Sun J., Fabbri M., Wayne A.S., Seeger R.C. Large-scale isolation and cytotoxicity of extracellular vesicles derived from activated human natural killer cells. J. Extracell. Vesicles, 2017, Vol. 6, no. 1, 1294368. doi: 10.1080/20013078.2017.1294368.Keerthikumar S., Gangoda L., Gho Y.S., Mathivanan S. Exosomes and microvesicles. Methods in molecular biology. Ed. Hill A., Humana Press, 2017, pp. 189-196.Keerthikumar S., Gangoda L., Gho Y.S., Mathivanan S. Exosomes and microvesicles. Methods in molecular biology. Ed. Hill A., Humana Press, 2017, pp. 189-196.Khurana D., Arneson L.N., Schoon R.A., Dick C.J., Leibson P.J. Differential regulation of human NK cellmediated cytotoxicity by the tyrosine kinase Itk. J. Immunol., 2007, Vol. 178, no. 6, pp. 3575-3582.Khurana D., Arneson L.N., Schoon R.A., Dick C.J., Leibson P.J. Differential regulation of human NK cellmediated cytotoxicity by the tyrosine kinase Itk. J. Immunol., 2007, Vol. 178, no. 6, pp. 3575-3582.Ko Y.H., Park S., Jin H., Woo H., Lee H., Park C., Kim K. Granzyme B leakage-induced apoptosis is a crucial mechanism of cell death in nasal-type NK/T-cell lymphoma. Lab. Invest., 2007, Vol. 87, no. 3, pp. 241-250.Ko Y.H., Park S., Jin H., Woo H., Lee H., Park C., Kim K. Granzyme B leakage-induced apoptosis is a crucial mechanism of cell death in nasal-type NK/T-cell lymphoma. Lab. Invest., 2007, Vol. 87, no. 3, pp. 241-250.Korenevskii A.V., Milyutina Y.P., Zhdanova A.A., Pyatygina K.M., Sokolov D.I., Sel’kov S.A. Massspectrometric analysis of proteome of microvesicles produced by NK-92 natural killer cells. Bull. Exp. Biol. Med., 2018, Vol. 165, no. 4, pp. 564-571.Korenevskii A.V., Milyutina Y.P., Zhdanova A.A., Pyatygina K.M., Sokolov D.I., Sel’kov S.A. Massspectrometric analysis of proteome of microvesicles produced by NK-92 natural killer cells. Bull. Exp. Biol. Med., 2018, Vol. 165, no. 4, pp. 564-571.Kumar D., Hosse J., von Toerne C., Noessner E., Nelson P.J. JNK MAPK pathway regulates constitutive transcription of CCL5 by human NK cells through SP1. J. Immunol., 2009, Vol. 182, no. 2, pp. 1011-1020.Kumar D., Hosse J., von Toerne C., Noessner E., Nelson P.J. JNK MAPK pathway regulates constitutive transcription of CCL5 by human NK cells through SP1. J. Immunol., 2009, Vol. 182, no. 2, pp. 1011-1020.Kweon S., Phan M.T., Chun S., Yu H., Kim J., Kim S., Lee J., Ali A.K., Lee S.H., Kim S.K., Doh J., Cho D. Expansion of human NK cells using K562 cells expressing OX40 ligand and short exposure to IL-21. Front. Immunol., 2019, Vol. 10, 879. doi: 10.3389/fimmu.2019.00879.Kweon S., Phan M.T., Chun S., Yu H., Kim J., Kim S., Lee J., Ali A.K., Lee S.H., Kim S.K., Doh J., Cho D. Expansion of human NK cells using K562 cells expressing OX40 ligand and short exposure to IL-21. Front. Immunol., 2019, Vol. 10, 879. doi: 10.3389/fimmu.2019.00879.Liu X.C., Liang H., Tian Z., Ruan Y.S., Zhang L., Chen Y. Proteomic analysis of human NK-92 cells after NK cell-mediated cytotoxicity against K562 cells. Biochemistry Moscow, 2007, Vol. 72, no. 7, pp. 716-727.Liu X.C., Liang H., Tian Z., Ruan Y.S., Zhang L., Chen Y. Proteomic analysis of human NK-92 cells after NK cell-mediated cytotoxicity against K562 cells. Biochemistry Moscow, 2007, Vol. 72, no. 7, pp. 716-727.Lugini L., Cecchetti S., Huber V., Luciani F., Macchia G., Spadaro F., Paris L., Abalsamo L., Colone M., Molinari A., Podo F., Rivoltini L., Ramoni C., Fais S. Immune surveillance properties of human NK cell-derived exosomes. J. Immunol., 2012, Vol. 189, no. 6, pp. 2833-2842.Lugini L., Cecchetti S., Huber V., Luciani F., Macchia G., Spadaro F., Paris L., Abalsamo L., Colone M., Molinari A., Podo F., Rivoltini L., Ramoni C., Fais S. Immune surveillance properties of human NK cell-derived exosomes. J. Immunol., 2012, Vol. 189, no. 6, pp. 2833-2842.Ma D., Cao W., Kapur A., Felder M., Scarlett C.O., Patankar M.S., Li L. Differential expression of proteins in naive and IL-2 stimulated primary human NK cells identified by global proteomic analysis. J. Proteomics, 2013, Vol. 91, pp. 151-163.Ma D., Cao W., Kapur A., Felder M., Scarlett C.O., Patankar M.S., Li L. Differential expression of proteins in naive and IL-2 stimulated primary human NK cells identified by global proteomic analysis. J. Proteomics, 2013, Vol. 91, pp. 151-163.Malloci M., Perdomo L., Veerasamy M., Andriantsitohaina R., Simard G., Martinez M.C. Extracellular vesicles: mechanisms in human health and disease. Antioxid. Redox Signal., 2019, Vol. 30, no. 6, pp. 813-856.Malloci M., Perdomo L., Veerasamy M., Andriantsitohaina R., Simard G., Martinez M.C. Extracellular vesicles: mechanisms in human health and disease. Antioxid. Redox Signal., 2019, Vol. 30, no. 6, pp. 813-856.Malorni W., Quaranta M.G., Straface E., Falzano L., Fabbri A., Viora M., Fiorentini C. The Rac-activating toxin cytotoxic necrotizing factor 1 oversees NK cell-mediated activity by regulating the actin/microtubule interplay. J. Immunol., 2003, Vol. 171, no. 8, pp. 4195-4202.Malorni W., Quaranta M.G., Straface E., Falzano L., Fabbri A., Viora M., Fiorentini C. The Rac-activating toxin cytotoxic necrotizing factor 1 oversees NK cell-mediated activity by regulating the actin/microtubule interplay. J. Immunol., 2003, Vol. 171, no. 8, pp. 4195-4202.Manzini C., Vene R., Cossu I., Gualco M., Zupo S., Dono M., Spagnolo F., Queirolo P., Moretta L., Mingari M.C., Pietra G. Cytokines can counteract the inhibitory effect of MEK-i on NK-cell function. Oncotarget, 2016, Vol. 7, no. 38, pp. 60858-60871.Manzini C., Vene R., Cossu I., Gualco M., Zupo S., Dono M., Spagnolo F., Queirolo P., Moretta L., Mingari M.C., Pietra G. Cytokines can counteract the inhibitory effect of MEK-i on NK-cell function. Oncotarget, 2016, Vol. 7, no. 38, pp. 60858-60871.Mizrahi S., Markel G., Porgador A., Bushkin Y., Mandelboim O. CD100 on NK cells enhance IFNgamma secretion and killing of target cells expressing CD72. PLoS ONE, 2007, Vol. 2, no. 9, e818. doi: 10.1371/journal.pone.0000818.Mizrahi S., Markel G., Porgador A., Bushkin Y., Mandelboim O. CD100 on NK cells enhance IFNgamma secretion and killing of target cells expressing CD72. PLoS ONE, 2007, Vol. 2, no. 9, e818. doi: 10.1371/journal.pone.0000818.Nawrot R., Barylski J., Schulze W.X. Incorrectly annotated keratin derived peptide sequences lead to misleading MS/MS data interpretation. J. Proteomics, 2013, Vol. 91, pp. 270-273.Nawrot R., Barylski J., Schulze W.X. Incorrectly annotated keratin derived peptide sequences lead to misleading MS/MS data interpretation. J. Proteomics, 2013, Vol. 91, pp. 270-273.Ochoa M.C., Minute L., Rodriguez I., Garasa S., Perez-Ruiz E., Inoges S., Melero I., Berraondo P. Antibodydependent cell cytotoxicity (ADCC): immunotherapy strategies enhancing effector NK cells. Immunol. Cell Biol., 2017, no. 4, pp. 347-355.Ochoa M.C., Minute L., Rodriguez I., Garasa S., Perez-Ruiz E., Inoges S., Melero I., Berraondo P. Antibodydependent cell cytotoxicity (ADCC): immunotherapy strategies enhancing effector NK cells. Immunol. Cell Biol., 2017, no. 4, pp. 347-355.Oykhman P., Timm-McCann M., Xiang R.F., Islam A., Li S.S., Stack D., Huston S.M., Ma L.L., Mody C.H. Requirement and redundancy of the Src family kinases Fyn and Lyn in perforin-dependent killing of Cryptococcus neoformans by NK cells. Infect. Immun., 2013, Vol. 81, no. 10, pp. 3912-3922.Oykhman P., Timm-McCann M., Xiang R.F., Islam A., Li S.S., Stack D., Huston S.M., Ma L.L., Mody C.H. Requirement and redundancy of the Src family kinases Fyn and Lyn in perforin-dependent killing of Cryptococcus neoformans by NK cells. Infect. Immun., 2013, Vol. 81, no. 10, pp. 3912-3922.Pesce S., Carlomagno S., Moretta A., Sivori S., Marcenaro E. Uptake of CCR7 by KIR2DS4(+) NK cells is induced upon recognition of certain HLA-C alleles. J. Immunol. Res., 2015, Vol. 2015, 754373. doi: 10.1155/2015/754373.Pesce S., Carlomagno S., Moretta A., Sivori S., Marcenaro E. Uptake of CCR7 by KIR2DS4(+) NK cells is induced upon recognition of certain HLA-C alleles. J. Immunol. Res., 2015, Vol. 2015, 754373. doi: 10.1155/2015/754373.Scheiter M., Lau U., van Ham M., Bulitta B., Grobe L., Garritsen H., Klawonn F., Konig S., Jansch L. Proteome analysis of distinct developmental stages of human natural killer (NK) cells. Mol. Cell. Proteomics, 2013, Vol. 12, no. 5, pp. 1099-1114.Scheiter M., Lau U., van Ham M., Bulitta B., Grobe L., Garritsen H., Klawonn F., Konig S., Jansch L. Proteome analysis of distinct developmental stages of human natural killer (NK) cells. Mol. Cell. Proteomics, 2013, Vol. 12, no. 5, pp. 1099-1114.Singh U.P., Singh S., Singh R., Cong Y., Taub D.D., Lillard J.W., Jr. CXCL10-producing mucosal CD4+ T cells, NK cells, and NKT cells are associated with chronic colitis in IL-10(-/-) mice, which can be abrogated by antiCXCL10 antibody inhibition. J. Interferon Cytokine Res., 2008, Vol. 28, no. 1, pp. 31-43.Singh U.P., Singh S., Singh R., Cong Y., Taub D.D., Lillard J.W., Jr. CXCL10-producing mucosal CD4+ T cells, NK cells, and NKT cells are associated with chronic colitis in IL-10(-/-) mice, which can be abrogated by antiCXCL10 antibody inhibition. J. Interferon Cytokine Res., 2008, Vol. 28, no. 1, pp. 31-43.Sokolov D.I., Markova K.L., Mikhailova V.A., Vyazmina L.P., Milyutina Y.P., Kozyreva A.R., Zhdanova A.A., Malygina D.A., Onokhin K.V., Ivanova A.N., Korenevsky A.V., Selkov S.A. Phenotypic and functional characteristics of microvesicles produced by natural killer cells. Medical Immunology (Russia), 2019, Vol. 21, no. 4, pp. 669-688. doi: 10.15789/1563-0625-2019-4-669-688.Sokolov D.I., Markova K.L., Mikhailova V.A., Vyazmina L.P., Milyutina Y.P., Kozyreva A.R., Zhdanova A.A., Malygina D.A., Onokhin K.V., Ivanova A.N., Korenevsky A.V., Selkov S.A. Phenotypic and functional characteristics of microvesicles produced by natural killer cells. Medical Immunology (Russia), 2019, Vol. 21, no. 4, pp. 669-688. doi: 10.15789/1563-0625-2019-4-669-688.Sokolov D.I., Ovchinnikova O.M., Korenkov D.A., Viknyanschuk A.N., Benken K.A., Onokhin K.V., Selkov S.A. Influence of peripheral blood microparticles of pregnant women with preeclampsia on the phenotype of monocytes. Transl. Res., 2016, Vol. 170, pp. 112-123.Sokolov D.I., Ovchinnikova O.M., Korenkov D.A., Viknyanschuk A.N., Benken K.A., Onokhin K.V., Selkov S.A. Influence of peripheral blood microparticles of pregnant women with preeclampsia on the phenotype of monocytes. Transl. Res., 2016, Vol. 170, pp. 112-123.Thery C., Zitvogel L., Amigorena S. Exosomes: composition, biogenesis and function. Nat. Rev. Immunol., 2002, Vol. 2, no. 8, pp. 569-579.Thery C., Zitvogel L., Amigorena S. Exosomes: composition, biogenesis and function. Nat. Rev. Immunol., 2002, Vol. 2, no. 8, pp. 569-579.Tramontano A.F., Lyubarova R., Tsiakos J., Palaia T., Deleon J.R., Ragolia L. Circulating endothelial microparticles in diabetes mellitus. Mediators Inflamm., 2010, Vol. 2010, 250476. doi: 10.1155/2010/250476.Tramontano A.F., Lyubarova R., Tsiakos J., Palaia T., Deleon J.R., Ragolia L. Circulating endothelial microparticles in diabetes mellitus. Mediators Inflamm., 2010, Vol. 2010, 250476. doi: 10.1155/2010/250476.van der Pol E., Coumans F.A., Grootemaat A.E., Gardiner C., Sargent I.L., Harrison P., Sturk A., van Leeuwen T.G., Nieuwland R. Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. Thromb. Haemost., 2014, Vol. 12, no. 7, pp. 1182-1192.van der Pol E., Coumans F.A., Grootemaat A.E., Gardiner C., Sargent I.L., Harrison P., Sturk A., van Leeuwen T.G., Nieuwland R. Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. Thromb. Haemost., 2014, Vol. 12, no. 7, pp. 1182-1192.van Helden M.J., Zaiss D.M., Sijts A.J. CCR2 defines a distinct population of NK cells and mediates their migration during influenza virus infection in mice. PLoS ONE, 2012, Vol. 7, no. 12, e52027. doi: 10.1371/journal.pone.0052027.van Helden M.J., Zaiss D.M., Sijts A.J. CCR2 defines a distinct population of NK cells and mediates their migration during influenza virus infection in mice. PLoS ONE, 2012, Vol. 7, no. 12, e52027. doi: 10.1371/journal.pone.0052027.van Niel G., d’Angelo G., Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol., 2018, Vol. 19, no. 4, pp. 213-228.van Niel G., d’Angelo G., Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol., 2018, Vol. 19, no. 4, pp. 213-228.Vasilopoulou E., Loubiere L.S., Lash G.E., Ohizua O., McCabe C.J., Franklyn J.A., Kilby M.D., Chan S.Y. Triiodothyronine regulates angiogenic growth factor and cytokine secretion by isolated human decidual cells in a cell-type specific and gestational age-dependent manner. Hum. Reprod., 2014, Vol. 29, no. 6, pp. 1161-1172.Vasilopoulou E., Loubiere L.S., Lash G.E., Ohizua O., McCabe C.J., Franklyn J.A., Kilby M.D., Chan S.Y. Triiodothyronine regulates angiogenic growth factor and cytokine secretion by isolated human decidual cells in a cell-type specific and gestational age-dependent manner. Hum. Reprod., 2014, Vol. 29, no. 6, pp. 1161-1172.Veerman R.E., Gucluler Akpinar G., Eldh M., Gabrielsson S. Immune cell-derived extracellular vesicles –functions and therapeutic applications. Trends Mol. Med., 2019, Vol. 25, no. 5, pp. 382-394.Veerman R.E., Gucluler Akpinar G., Eldh M., Gabrielsson S. Immune cell-derived extracellular vesicles –functions and therapeutic applications. Trends Mol. Med., 2019, Vol. 25, no. 5, pp. 382-394.Voigt J., Malone D.F.G., Dias J., Leeansyah E., Bjorkstrom N.K., Ljunggren H.G., Grobe L., Klawonn F., Heyner M., Sandberg J.K., Jansch L. Proteome analysis of human CD56neg NK cells reveals a homogeneous phenotype surprisingly similar to CD56dim NK cells. Eur. J. Immunol., 2018, Vol. 48, no. 9, pp. 1456-1469.Voigt J., Malone D.F.G., Dias J., Leeansyah E., Bjorkstrom N.K., Ljunggren H.G., Grobe L., Klawonn F., Heyner M., Sandberg J.K., Jansch L. Proteome analysis of human CD56neg NK cells reveals a homogeneous phenotype surprisingly similar to CD56dim NK cells. Eur. J. Immunol., 2018, Vol. 48, no. 9, pp. 1456-1469.Wagstaffe H.R., Nielsen C.M., Riley E.M., Goodier M.R. IL-15 promotes polyfunctional NK cell responses to influenza by boosting IL-12 production. J. Immunol., 2018, Vol. 200, no. 8, pp. 2738-2747.Wagstaffe H.R., Nielsen C.M., Riley E.M., Goodier M.R. IL-15 promotes polyfunctional NK cell responses to influenza by boosting IL-12 production. J. Immunol., 2018, Vol. 200, no. 8, pp. 2738-2747.Wang W., Guo H., Geng J., Zheng X., Wei H., Sun R., Tian Z. Tumor-released galectin-3, a soluble inhibitory ligand of human NKp30, plays an important role in tumor escape from NK cell attack. J. Biol. Chem., 2014, Vol. 289, no. 48, pp. 33311-33319.Wang W., Guo H., Geng J., Zheng X., Wei H., Sun R., Tian Z. Tumor-released galectin-3, a soluble inhibitory ligand of human NKp30, plays an important role in tumor escape from NK cell attack. J. Biol. Chem., 2014, Vol. 289, no. 48, pp. 33311-33319.Zhu L., Aly M., Kuon R.J., Toth B., Wang H., Karakizlis H., Weimer R., Morath C., Ibrahim E., Ekpoom N., Opelz G., Daniel V. Patients with idiopathic recurrent miscarriage have abnormally high TGFss+ blood NK, NKT and T cells in the presence of abnormally low TGFss plasma levels. BMC Immunol., 2019, Vol. 20, no. 1, 10. doi: 10.1186/s12865-019-0290-3.Zhu L., Aly M., Kuon R.J., Toth B., Wang H., Karakizlis H., Weimer R., Morath C., Ibrahim E., Ekpoom N., Opelz G., Daniel V. Patients with idiopathic recurrent miscarriage have abnormally high TGFss+ blood NK, NKT and T cells in the presence of abnormally low TGFss plasma levels. BMC Immunol., 2019, Vol. 20, no. 1, 10. doi: 10.1186/s12865-019-0290-3.

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