References

mimmun

Медицинская иммунология

Medical Immunology (Russia)

1563-06252313-741X

SPb RAACI

10.15789/1563-0625-IPO-2216

mimmun-2216

Research Article

ОБЗОРЫ

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Иммунобиологические свойства гранулоцитарно-макрофагального колониестимулирующего фактора и синтетических пептидов его активного центра

Immunobiological properties of granulocytemacrophage colony-stimulating factor and synthetic peptides of his active center

https://orcid.org/0000-0003-4371-4161

Зурочка

А. В.

Zurochka

A. V.

Зурочка Александр Владимирович — доктор медицинских наук, профессор, ведущий научный сотрудник ИИФ УрО РАН; профессор кафедры «Пищевые биотехнологии», заведующий лабораторией иммунобиотехнологии ЮУрГУ (НИУ).

Екатеринбург; Челябинск.

Aleksandr V. Zurochka - PhD, MD (Medicine), Professor, Leading Research Associate, Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences; Professor, Department of Food Biotechnology, Head, Laboratory of Immunobiotechnolog, South-Ural State University (National Research University).

Yekaterinburg; Chelyabinsk.

av_zurochka@mail.ru

https://orcid.org/0000-0001-8930-3742

Зурочка

В. А.

Zurochka

V. A.

Зурочка Владимир Александрович — доктор медицинских наук, старший научный сотрудник лаборатории иммунологии воспаления ИИФ УрО РАН; профессор кафедры «Пищевые биотехнологии», старший научный сотрудник лаборатории иммунобиотехнологии ЮУрГУ (НИУ).

Екатеринбург; Челябинск.

Vladimir A. Zurochka - PhD, MD (Medicine), Professor, Senior Research Associate, Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences; Professor, Department of Food Biotechnology, Senior Research Associate, Laboratory of Immunobiotechnology South-Ural State University (National Research University).

Yekaterinburg; Chelyabinsk.

v_zurochka@mail.ru

https://orcid.org/0000-0003-1852-9650

Добрынина

М. А.

Dobrynina

M. A.

Добрынина Мария Александровна — кандидат медицинских наук, младший научный сотрудник лаборатории иммунологии воспаления.

620049, Екатеринбург, ул. Первомайская, 106.

Тел.: 8 (982) 340-40-00.

Maria A. Dobrynina - Junior Research Associate, Laboratory of Immunology of Inflammation, Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences.

620049, Yekaterinburg, Pervomayskaya str., 106.

Phone: 7 (982) 340-40-00.

mzurochka@mail.ru

https://orcid.org/0000-0002-2086-5170

Гриценко

В. А.

Gritsenko

V. A.

Гриценко Виктор Александрович — доктор медицинских наук, профессор, главный научный сотрудник лаборатории персистенции и симбиоза микроорганизмов.

Оренбург.

Viktor A. Gritsenko - PhD, MD (Medicine), Professor, Chief Research Associate, Laboratory of Persistence and Symbiosis of Microorganisms, Institute of Cellular and Intracellular Symbiosis, Ural Branch, Russian Academy of Sciences, Orenburg Federal Research Center, Ural Branch, Russian Academy of Sciences.

Orenburg.

vag59@mail.ru

Институт иммунологии и физиологии Уральского отделения Российской академии наук; Южно-Уральский государственный университет (национальный исследовательский университет)РоссияInstitute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences; South-Ural State University (National Research University)Russian Federation

Институт иммунологии и физиологии» Уральского отделения Российской академии наукРоссияInstitute of Immunology and Physiology, Ural Branch, Russian Academy of SciencesRussian Federation

Институт клеточного и внутриклеточного симбиоза Уральского отделения Российской академии наук ФГБУН «Оренбургский федеральный исследовательский центр Уральского отделения Российской академии наук»РоссияInstitute of Cellular and Intracellular Symbiosis, Ural Branch, Russian Academy of SciencesRussian Federation

2021

15112021

23510311054

2021

Зурочка А.В., Зурочка В.А., Добрынина М.А., Гриценко В.А.

Zurochka A.V., Zurochka V.A., Dobrynina M.A., Gritsenko V.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/2216

Гранулоцитарно-макрофагальный колониестимулирующий фактор (ГМ-КСФ; англ. GM-CSF — granulocyte-macrophage colony-stimulating factor) относится к группе ростовых цитокинов (гемопоэтинов), регулирующих пролиферацию и дифференциацию клеток миелоидного диферона. В последнее время накопилось много новых данных, указывающих на наличие у ГМ-КСФ и синтетических пептидов его активного центра ряда неизвестных ранее биологических эффектов, что отрывает новые перспективы для их широкого клинического использования.

В обзоре изложены современные представления о структуре, функциях и механизмах действия ГМ-КСФ и рассмотрена структура его рецептора. Охарактеризованы клетки-продуценты ГМ-КСФ и представлены клетки-мишени (эффекторные клетки), отвечающие на воздействие этого цитокина. Описаны известные внутриклеточные механизмы передачи сигнала при взаимодействии ГМ-КСФ с рецептором. Охарактеризованы основные плейотропные эффекты данного цитокина как фактора гемопоэза и иммуностимулирующего средства. Отражены известные и недавно обнаруженные иммунобиологические эффекты данного цитокина, его рекомбинантных форм и синтетических аналогов его активного центра.

Охарактеризовано участие ГМ-КСФ в гемопоэзе и дифференцировке миелоидных клеток, влияние данного цитокина на функциональную активность иммунокомпетентных (лимфоциты, макрофаги, нейтрофилы, дендритные клетки) и тканевых клеток. Изучено влияние ГМ-КСФ на развитие и течение инфекционно-воспалительных процессов, роль его в создании комбинированных вакцин. Представлены материалы по клиническому использованию ГМ-КСФ и его рекомбинантных форм в гематологии, иммунологии, онкологии, репродуктологии и при лечении системных аутоиммунных процессов и заболеваний инфекционной природы.

Авторами обобщены недавно обнаруженные иммунобиологические свойства синтетических пептидов активного центра ГМ-КСФ, свидетельствующие о наличии у них иммунотропных и гемопоэтических эффектов, а также антимикробной активности в отношении грамотрицательных и грам-положительных бактерий, вирусов и репарационного потенциала (влияние на скорость заживления раневого процесса), не характерных для цельной молекулы ГМ-КСФ. Проанализированы перспективы клинического применения синтетического аналога ГМ-КСФ (пептид ZP2) и возможности создания на его основе новых косметических средств и лекарственных препаратов, обладающих комбинированными иммуностимулирующими, антимикробными и репарационными свойствами.

Обзор расширяет взгляд на возможности цитокинотерапии при лечении различных заболеваний человека инфекционной и неинфекционной природы и ориентирован на широкий круг специалистов, работающих в области аллергологии и иммунологии, инфектологии и репарационной медицины.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) belongs to the group of growth cytokines (hematopoietins) that regulate proliferation and differentiation of myeloid lineage cells. Recently, a lot of new data have accumulated, indicating the presence of a number of previously unknown biological effects in GM-CSF and synthetic peptides of its active center, which open up new prospects for their wide clinical use.

The review outlines current understanding of the structure, functions, and mechanisms of GM-CSF action and concerns the structure of its receptor. The GM-CSF producer cells are characterized, as well as target cells (effector cells) responding to this cytokine are also presented. The known mechanisms of intracellular signaling involved into the GM-CSF/receptor interaction are described. The main pleiotropic effects of this cytokine as a factor of hematopoiesis and an immunostimulating agent are characterized. The previously known and recently found immunobiological effects of this cytokine, its recombinant forms and synthetic analogues of its active center are discussed.

Participation of GM-CSF in hematopoiesis and differentiation of myeloid cells, the effects of this cytokine on the functional activity of immunocompetent populations (lymphocytes, macrophages, neutrophils, dendritic cells) and tissue cells were characterized. The influence of GM-CSF on the development and course of infectious and inflammatory processes, its role in the creation of combined vaccines is reviewed. Clinical data on usage of GM-CSF and its recombinant forms in hematology, immunology, oncology, reproductive medicine and in the treatment of systemic autoimmune processes and infectious diseases are presented.

The recently discovered immunobiological properties of synthetic peptides derived from active center of GM-CSF are summarized, indicating that they exhibit immunotropic and hematopoietic effects, as well as antimicrobial activity against Gram-negative and Gram-positive bacteria, viruses, and tissue repair (effect on the rate of wound healing), which is not typical to the whole GM-CSF molecule. We discuss the prospects for clinical applications of synthetic GM-CSF analogue (ZP2 peptide), and an opportunity of creating new cosmetics and pharmaceuticals with combined immunostimulating, antimicrobial and reparative properties on its basis.

The review expands the view on potential usage of cytokine therapy in the treatment of various infectious and non-infectious diseases in humans, and is addressing a wide range of specialists working in the field of allergology and immunology, infectology and regenerative medicine.

гранулоцитарно-макрофагальный колониестимулирующий факторсинтетический пептид активного центрарецептор ГМ-КСФиммунобиологические эффектытерапия

granulocyte-macrophage colony-stimulating factorsynthetic peptide of the active centerGM-CSF-receptorimmunobiological effectstherapy

Работа выполнена по теме Плана НИР ИИФ УрО РАН, № гос. регистрации АААА-А18-118020690020-1, и теме Плана НИР ОФИЦ УрО РАН (ИКВС УрО РАН), № гос. регистрации 116021510075.

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