ФЕНОТИПИЧЕСКИЕ И ФУНКЦИОНАЛЬНЫЕ ХАРАКТЕРИСТИКИ МИКРОВЕЗИКУЛ, ПРОДУЦИРУЕМЫХ NK-КЛЕТКАМИ

Среди множества клеток-источников микровезикул (МВ) особый интерес представляют естественные киллеры (NK-клетки) - субпопуляция лимфоцитов, осуществляющая контактный цитолиз вирус-инфицированных и опухолевых клеток. Каждая из популяций NK-клеток обладает уникальным репертуаром рецепторов на своей поверхности, а, следовательно, и функциями. Функционирование NK-клеток регулируется широким диапазоном активирующих и ингибирующих рецепторов, которые экспрессируются на их поверхности. Экзоцитоз содержимого литических гранул при контакте с клеткой мишенью – самый распространённый механизм цитолиза мишени NK-клетками. В настоящее время имеются косвенные данные о способности NK-клеток продуцировать МВ, так как такие МВ с фенотипом CD56, а также МВ лейкоцитарного происхождения с различным фенотипом обнаружены в плазме периферической крови. Целью настоящего исследования явилось изучение фенотипа, состава и функциональной активности микровезикул, образуемых NK-клетками. Сравнительный анализ спонтанной экспрессии рецепторов при помощи проточной цитофлуориметрии показал, что МВ, как и клетки-источники (NK-клетки линии NK-92), обладают сходным профилем экспрессии молекул CD56 и CD16, но отличаются более выраженной экспрессией CD119 и CD11b и менее выраженной экспрессией CD18. Культивирование клеток линии NK-92 в присутствии индукторов (TNFα, IL-1β, IFNγ, PMA) приводило к изменению фенотипа как самих клеток, так и МВ, образуемых ими. По данным проведенного WesternBlot Analisis в присутствии указанных индукторов также изменялось содержание перфорина и гранзима B (GrB) в составе МВ. Анализ цитотоксической активности клеток линии NK-92 в отношении клеток линии K562 показал, что МВ, полученные от активированных TNFα клеток линии NK-92 повышают цитотоксичность активированных же TNFα клеток линии NK-92 по сравнению с уровнем их цитотоксичности в отношении клеток линии K562 без МВ, что совпадает с обнаруженным нами повышенным содержанием GrB в МВ, полученных от активированных TNFα клеток линии NK-92. Суммируя полученные данные следует отметить, что в зависимости от типа индуктора NK-клетки линии NK-92 продуцируют микрочастицы разные по фенотипу и составу. Изменение состава МВ может приводить к изменению их функциональной активности, в частности, к усилению цитотоксической активности NK-клеток.

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