Engin Atilla
Department of General Surgery, Faculty of Medicine, Gazi University, Ankara, Turkey.
Adv Exp Med Biol. 2021;1275:101-131. doi: 10.1007/978-3-030-49844-3_4.
Exosomes are nanoscale extracellular vesicles that can transport cargos of proteins, lipids, DNA, various RNA species and microRNAs (miRNAs). Exosomes can enter cells and deliver their contents to recipient cell. Owing to their cargo exosomes can transfer different molecules to the target cells and change the phenotype of these cells. The fate of the contents of an exosome depends on its target destination. Various mechanisms for exosome uptake by target cells have been proposed, but the mechanisms responsible for exosomes internalization into cells are still debated. Exosomes exposed cells produce labeled protein kinases, which are expressed by other cells. This means that these kinases are internalized by exosomes, and transported into the cytoplasm of recipient cells. Many studies have confirmed that exosomes are not only secreted by living cells, but also internalized or accumulated by the other cells. The "next cell hypothesis" supports the notion that exosomes constitute communication vehicles between neighboring cells. By this mechanism, exosomes participate in the development of diabetes and its associated complications, critically contribute to the spreading of neuronal damage in Alzheimer's disease, and non-proteolysed form of Fas ligand (mFasL)-bearing exosomes trigger the apoptosis of T lymphocytes. Furthermore, exosomes derived from human B lymphocytes induce antigen-specific major histocompatibility complex (MHC) class II-restricted T cell responses. Interestingly, exosomes secreted by cancer cells have been demonstrated to express tumor antigens, as well as immune suppressive molecules. This process is defined as "exosome-immune suppression" concept. The interplay via the exchange of exosomes between cancer cells and between cancer cells and the tumor stroma promote the transfer of oncogenes and onco-miRNAs from one cell to other. Circulating exosomes that are released from hypertrophic adipocytes are effective in obesity-related complications. On the other hand, the "inflammasome-induced" exosomes can activate inflammatory responses in recipient cells. In this chapter protein kinases-related checkpoints are emphasized considering the regulation of exosome biogenesis, secretory traffic, and their impacts on cell death, tumor growth, immune system, and obesity.
外泌体是纳米级的细胞外囊泡，能够运输蛋白质、脂质、DNA、各种RNA种类以及微小RNA（miRNA）等物质。外泌体可以进入细胞并将其内容物传递给受体细胞。由于其携带的物质，外泌体能够将不同分子转移到靶细胞并改变这些细胞的表型。外泌体内容物的命运取决于其靶标目的地。已经提出了多种靶细胞摄取外泌体的机制，但外泌体内化进入细胞的具体机制仍存在争议。暴露于外泌体的细胞会产生由其他细胞表达的标记蛋白激酶。这意味着这些激酶被外泌体内化，并运输到受体细胞的细胞质中。许多研究证实，外泌体不仅由活细胞分泌，还会被其他细胞内化或积累。“下一个细胞假说”支持外泌体构成相邻细胞间通讯载体的观点。通过这种机制，外泌体参与糖尿病及其相关并发症的发展，在阿尔茨海默病中对神经元损伤的扩散起关键作用，并且携带非蛋白水解形式的Fas配体（mFasL）的外泌体会触发T淋巴细胞的凋亡。此外，源自人类B淋巴细胞的外泌体可诱导抗原特异性的主要组织相容性复合体（MHC）II类限制性T细胞反应。有趣的是，癌细胞分泌的外泌体已被证明可表达肿瘤抗原以及免疫抑制分子。这一过程被定义为“外泌体免疫抑制”概念。癌细胞之间以及癌细胞与肿瘤基质之间通过外泌体交换的相互作用促进了癌基因和致癌miRNA从一个细胞向另一个细胞的转移。肥大脂肪细胞释放的循环外泌体在肥胖相关并发症中起作用。另一方面，“炎症小体诱导的”外泌体可激活受体细胞中的炎症反应。在本章中，考虑到外泌体生物发生、分泌运输及其对细胞死亡、肿瘤生长、免疫系统和肥胖的影响，强调了与蛋白激酶相关的检查点。
