Denzer K, Kleijmeer M J, Heijnen H F, Stoorvogel W, Geuze H J
Department of Cell Biology, Institute of Biomembranes and Centre for Biomedical Genetics, University Medical Center Utrecht, The Netherlands.
J Cell Sci. 2000 Oct;113 Pt 19:3365-74. doi: 10.1242/jcs.113.19.3365.
Exosomes are small membrane vesicles that are secreted by a multitude of cell types as a consequence of fusion of multivesicular late endosomes/lysosomes with the plasma membrane. Depending on their origin, exosomes can play roles in different physiological processes. Maturing reticulocytes externalize obsolete membrane proteins such as the transferrin receptor by means of exosomes, whereas activated platelets release exosomes whose function is not yet known. Exosomes are also secreted by cytotoxic T cells, and these might ensure specific and efficient targeting of cytolytic substances to target cells. Antigen presenting cells, such as B lymphocytes and dendritic cells, secrete MHC class-I- and class-II-carrying exosomes that stimulate T cell proliferation in vitro. In addition, dendritic-cell-derived exosomes, when used as a cell-free vaccine, can eradicate established murine tumors. Although the precise physiological target(s) and functions of exosomes remain largely to be resolved, follicular dendritic cells (accessory cells in the germinal centers of secondary lymphoid organs) have recently been shown to bind B-lymphocyte-derived exosomes at their cell surface, which supports the notion that exosomes play an immunoregulatory role. Finally, since exosomes are derived from multivesicular bodies, their molecular composition might provide clues to the mechanism of protein and lipid sorting in endosomes.
外泌体是一种小的膜泡,由多种细胞类型分泌,其产生是由于多囊泡晚期内体/溶酶体与质膜融合的结果。根据其来源,外泌体可在不同的生理过程中发挥作用。成熟的网织红细胞通过外泌体将诸如转铁蛋白受体等过时的膜蛋白排出细胞外,而活化的血小板则释放功能尚不清楚的外泌体。细胞毒性T细胞也会分泌外泌体,这些外泌体可能确保溶细胞物质特异性且高效地靶向靶细胞。抗原呈递细胞,如B淋巴细胞和树突状细胞,会分泌携带MHC-I类和II类分子的外泌体,这些外泌体在体外可刺激T细胞增殖。此外,树突状细胞来源的外泌体用作无细胞疫苗时,可根除已形成的小鼠肿瘤。尽管外泌体的确切生理靶点和功能在很大程度上仍有待确定,但滤泡树突状细胞(二级淋巴器官生发中心的辅助细胞)最近被证明可在其细胞表面结合B淋巴细胞来源的外泌体,这支持了外泌体发挥免疫调节作用的观点。最后,由于外泌体来源于多囊泡体,其分子组成可能为内体中蛋白质和脂质分选机制提供线索。