Макрофаги М1/М2: происхождение, фенотип, способы получения, взаимодействие с естественными киллерами и трофобластом

В настоящем обзоре представлены современные данные о происхождении моноцитов/ макрофагов, условиях, необходимых для дифференцировки моноцитов в макрофаги М1 или М2. Описаны три субпопуляции моноцитов периферической крови: 1) классические – основная субпопуляция (85-90%), эффективно осуществляющая фагоцитоз; 2) промежуточные моноциты (5-10%) – участвуют в процессинге и презентации антигена, в ангиогенезе, восстановлении эндотелия сосудов; 3) неклассические моноциты (10%) – «патрулируют» сосудистую сеть, удаляют клеточный дебрис, участвуют в ремоделировании тканей. В обзоре приведены подробные характеристики для каждого подкласса макрофагов: провоспалительные (М1) и противовоспалительные (М2), играющие разные роли в инициации и разрешении воспаления; описаны их фенотип, спектр секретируемых цитокинов, экспрессия транскрипционных факторов, выполняемые функции. Для популяции М2 подробно описаны особенности субпопляции: М2a, М2b, М2c, М2d. В обзоре приведены методы и подходы к получению поляризованных макрофагов в условиях in vitro как из моноцитов периферической крови, так и из клеток перевиваемых культур, основанные на сигналах, получаемых макрофагами в условиях in vivo; приведены фенотип, продукция цитокинов и функциональные свойства искусственно поляризованных макрофагов в зависимости от условий их получения. В обзоре подробно рассматриваются особенности контактного и дистантного взаимодействия макрофагов различных подклассов с клетками микроокружения на примере естественных киллеров и клеток трофобласта, приводятся сведения об изменении фенотипа, транскрипционного и секреторного профиля взаимодействующих клеток. Описаны механизмы контроля трофобластом дифференцировки макрофагов в уникальную М2-популяцию децидуальных макрофагов, контролирующих как развитие и функционирование трофобласта, так и его апоптоз. В обзоре подробно рассматриваются известные на сегодняшний день варианты взаимодействия субпопуляций макрофагов с естественными киллерами. Влияние Мϕ на NK-клетки проявляется в изменении экспрессии последними транскрипционных факторов, определяющих не только их дифференцировку, но и функциональную активность. Макрофаги рассматриваются как клетки, активно влияющие на функциональное состояние и дифференцировку естественных киллеров. В обзоре рассматриваются механизмы взаимоотношений всех трех типов клеток: макрофагов, трофобласта и естественных киллеров в зоне маточно-плацентарного контакта. Изучение взаимодействий этих клеток прольет свет не только на особенности межклеточных взаимоотношений в зоне маточно-плацентарного контакта, но и на взаимоотношения клеток опухолей с NK-клетками и макрофагами.

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