Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI7510.15789/2220-7619-2012-3-597-602REVIEWSОБЗОРЫSAPOSIN-LIKE PROTEINS IN ANTI-INFECTIOUS IMMUNE RESPONSEСАПОЗИН-ПОДОБНЫЕ БЕЛКИ В ПРОТИВОИНФЕКЦИОННОМ ИММУННОМ ОТВЕТЕYeremeevV. V.ЕремеевВ. В.
Russian Federation

д.м.н., ведущий научный сотрудник лаборатории иммуногенетики

107564, Москва, Яузская аллея, 2

yeremeev56@mail.ruAptA. S.АптА. С.
Russian Federation
yeremeev56@mail.ruЦентральный НИИ туберкулеза РАМН, Москва02072012235976020207201402072014Copyright ©; 2014, Yeremeev V.V., Apt A.S.Copyright ©; 2014, Еремеев В.В., Апт А.С.2014Yeremeev V.V., Apt A.S.Еремеев В.В., Апт А.С.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/75

Abstract. Besides the multiple hydrolytic enzymes, lysosomes are equipped with proteins apt to activate sphyngo-lipids — saposins (SAP). SAP belong to a broad and diverse family of moderate-size (~80 AA) saposin-like proteins (SAPLIP) containing specific domains with three disulfid e bonds bridging six cysteine residues. The diversity of SAPLIPS is likely explained by their involvement in distinct phases of engulfed bacteria digesting. Functionally similar SAPLIP were identified in a wide range of species — from amoeba to mammals, including humans. Saposins per se form a subfamily with six members: saposins A-D and the protein GM2 which possesses activatory functions. SAP do not have enzymatic activity, are heat-stable and protease resistant. The major in vivo function of SAP is released via participation in sphyngolipid catabolism and membrane digestion. In addition, complex association of SAP with membrane bi-layer and CD1 glycolipids is essential for loading lipid antigens onto antigen-presenting CD1 molecules for subsequent activation of lipid-specific T-cells. Of particular interest is participation of SAP in cross-presentation of bacterial antigens to CD8+ T-cells. A broad spectrum of SAP and SAPLIP involvement in the reactions of innate and adaptive immunity indicates their evolutionary conserved role in host defense.

Резюме. Помимо множества гидролитических ферментов, лизосомы оснащены белками-активаторами сфинголипидов — сапозинами (SAP). SAP принадлежат к обширному и разнообразному семейству небольших (~80 аминокислотных остатков) сапозин-подобных белков (SAPLIP), содержащих характерные домены с тремя дисульфидными связями между шестью остатками цистеина. Разнообразие известных SAPLIP можно объяснить их участием в различных этапах переваривания фагоцитированных бактерий. Сходные по функциям SAPLIP обнаружены как у простейших (амебы), так и у млекопитающих, в том числе у человека. К собственно сапозинам относят пять молекул сапозинов (A-D) и белок-активатор GM2. SAP не обладают ферментативной активностью, термостабильны и устойчивы к действию протеаз. Основная функция SAP в организме — участие в катаболизме сфинголипидов и переваривании мембран. Кроме того, сложная ассоциация сапозинов с двойным слоем липидов мембраны и гликопротеинов CD1 обеспечивает загрузку липидных антигенов на презентирующие молекулы CD1 для последующей активации специфичных к липидным антигенам Т-клеток. Особый интерес представляет участие сапозинов в механизмах перекрестной презентации бактериальных антигенов Т-клеткам CD8+. Широкая вовлеченность сапозинов и сапозин-подобных белков в механизмы врожденного и адаптивного иммунных ответов предполагает их эволюционно-консервативную роль в противомикробной защите.

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