Физиологическая и патогенетическая роль рецепторов-мусорщиков у человека

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.

рецепторы-мусорщики, тканевой стресс, поляризация макрофагов, хроническое воспаление низкой интенсивности, атеросклероз, опухолевые заболевания, нейродегенерация, системное воспаление

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