mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-PAP-1893mimmun-1893Research ArticleОБЗОРЫREVIEWSФизиологическая и патогенетическая роль рецепторов-мусорщиков у человекаPhysiological and pathogenic role of scavenger receptors in humansГусевЕ. Ю.GusevE. Yu.

Гусев Е.Ю. – д.м.н., профессор, заведующий лабораторией иммунологии воспаления

г. Екатеринбург

Gusev E.Yu., PhD, MD (Medicine), Professor, Head, Laboratory of Inflammation Immunology

Ekaterinburg

noemail@elpub.ruhttps://orcid.org/0000-0001-9788-1243ЗотоваН. В.ZotovaN. V.

Зотова Н.В. – к.б.н., старший научный сотрудник; доцент кафедры медицинской биохимии и биофизики

620049, г. Екатеринбург, ул. Первомайская, 106

Zotova N.V., PhD (Biology), Senior Research Associate; Associate Professor, Department of Medical Biochemistry and Biophysics

620049, Ekaterinburg, Pervomayskaya str., 106.

zotovanat@mail.ruЖуравлеваЮ. А.ZhuravlevaYu. A.

Журавлева Ю.А. – к.б.н., старший научный сотрудник лаборатории иммунологии воспаления 

г. Екатеринбург

Zhuravleva Yu.A., PhD (Biology), Senior Research Associate, Laboratory of Inflammation Immunology

Ekaterinburg

noemail@elpub.ruЧерешневВ. А.ChereshnevV. A.

Черешнев В.А. – д.м.н., профессор, академик РАН, научный руководитель

г. Екатеринбург

Chereshnev V.A., PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Research Director

Ekaterinburg

noemail@elpub.ruФГБУН «Институт иммунологии и физиологии» Уральского отделения Российской академии наукРоссияInstitute of Immunology and Physiology, Ural Branch, Russian Academy of SciencesRussian FederationФГБУН «Институт иммунологии и физиологии» Уральского отделения Российской академии наук; ФГАОУ ВО «Уральский федеральный университет имени первого Президента России Б.Н. Ельцина»РоссияInstitute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences; B. Eltsin Ural Federal UniversityRussian Federation202029012020221748Copyright © Гусев Е.Ю., Зотова Н.В., Журавлева Ю.А., Черешнев В.А., 20202020Гусев Е.Ю., Зотова Н.В., Журавлева Ю.А., Черешнев В.А.Gusev E.Y., Zotova N.V., Zhuravleva Y.A., Chereshnev 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/1893

Рецепторы мусорщики – SR (scavenger receptor) включают более 30 отдельных представителей, разделенных по структурному принципу на 11 классов (A-L). Они экспрессируются преимущественно на стромальных макрофагах, их экспрессия на клетках может увеличиваться в прямой зависимости от концентрации их лигандов. По своему строению SR гетерогенны, но их объединяет общая функциональная направленность. Так, различные классы SR могут участвовать в поглощении модифицированных липопротеинов низкой плотности, гликированных белков, апоптозных, стареющих и поврежденных клеток, измененных эритроцитов и тромбоцитов, а также большого числа других эндогенных лигандов из разряда метаболического и клеточного «мусора». Также общим свойством SR является их участие в удалении из кровотока и других тканей относительно небольших количеств патогенов, регулирование процессов клеточного и тканевого стресса, способность образовывать сложные рецепторные комплексы с другими типами рецепторов, включая интегрины и Toll-подобные рецепторы. В отличие от классических паттерн-распознающих рецепторов (ПРР), задействование SR не всегда приводит к выраженной активации клеток и развитию провоспалительного клеточного стресса. Функциональные эффекты SR обеспечивают взаимосвязь различных физиологических процессов с иммунной системой, включая процессы нейроэндокринной и метаболической регуляции. Эти механизмы не только обеспечивают стабильность гомеостаза, но также лежат на границе нормы и патологии, участвуя в патогенезе переходных состояний, а также в процессах физиологического старения. Одновременно с этим связанные с SR процессы являются одними из ключевых факторов патогенеза различных соматических заболеваний, в том числе ассоциированных с хроническим воспалением низкой интенсивности, включая ожирение, диабет 2-го типа, атеросклероз, гипертонию, различные варианты нейродегенерации. Также SR вовлечены в процессы опухолевой трансформации и противоопухолевого иммунитета, в различные процессы классического воспаления, начиная с презентации антигенов и заканчивая процессами морфофункциональной поляризации макрофагов и Т-клеток в очаге воспаления и иммунокомпетентных органов. SR играют противоречивую роль в развитии острого системного воспаления – главную причину летальных исходов в палатах интенсивной терапии. Целенаправленное воздействие на SR является перспективным направлением терапии очень широкого круга заболеваний, а определение мембранных и растворимых форм SR – методами диагностики и мониторинга многих патологий человека.

The scavenger receptors (SRs)) include > 30 different molecules structurally classified into 11 classes (A to L). They are expressed mostly on stromal macrophages, and their expression may be augmented in direct dependence with concentrations of their ligands. The SRs are heterogenous by their structure, however, being common in their functional potential. E.g., different SR classes may participate in absorption of modified low-density lipoproteins and glycated proteins, apoptotic and ageing cells, altered erythrocytes and platelets, like as a big variety of other endogenous ligands from metabolic and cellular “trash”. A common property of SRs is their participation in removal of small pathogen amounts from blood circulation, regulation of cell and tissue stress responses, ability to form complicated receptor complexes with other receptor types including integrins and toll-like receptors. Opposite to classic pattern-recognizing receptors, the SR involvement does not always elicit a pronounced cellular activation and development of pro-inflammatory cellular stress. The SR functional effects provide interactions between different physiological events and immune system, including the processes of neuroendocrine and metabolic regulation. These mechanisms provide both homeostatic stability and, likewise, act at the border of normal and pathological conditions, i.e., participating in pathogenesis of transitional processes, e.g., physiological ageing. Moreover, the SR-associated processes represent a key pathogenetic factor in different somatic diseases, e.g., those associated with low-intensity chronic inflammation, including obesity, type 2 diabetes, atherosclerosis, arterial hypertension, various neurodegenerative disorders. Similarly, the SRs are involved into the processes of cancer transformation and antitumor response, different processes of classical inflammation, from antigen presentation to the morphofunctional T cell and macrophage polarization in the inflammation foci and immunocompetent organs. SR are playing a controversial role in development of acute systemic inflammation, the main reason for lethal outcomes in the intensive care wards. Targeted effects upon the SRs represent a promising approach when treating a broad variety of diseases, whereas detection of membrane-bound and soluble SR forms could be performed by means of diagnostic and monitoring techniques in many human disorders.

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