Munich Stephan, Sobo-Vujanovic Andrea, Buchser William J, Beer-Stolz Donna, Vujanovic Nikola L
Department of Pathology; University of Pittsburgh Cancer Institute; Pittsburgh, PA USA ; Rush University Medical Center; Department of Neurosurgery; Chicago, IL USA.
Oncoimmunology. 2012 Oct 1;1(7):1074-1083. doi: 10.4161/onci.20897.
Autocrine and paracrine cell communication can be conveyed by multiple mediators, including membrane-associate proteins, secreted proteins and exosomes. Exosomes are 30-100 nm endosome-derived vesicles consisting in cytosolic material surrounded by a lipid bilayer containing transmembrane proteins. We have previously shown that dendritic cells (DCs) express on their surface multiple TNF superfamily ligands (TNFSFLs), by which they can induce the apoptotic demise of tumor cells as well as the activation of natural killer (NK) cells. In the present study, we demonstrate that, similar to DCs, DC-derived exosomes (DCex) express on their surface TNF, FasL and TRAIL, by which they can trigger caspase activation and apoptosis in tumor cells. We also show that DCex activate NK cells and stimulate them to secrete interferonγ (IFNγ) upon the interaction of DCex TNF with NK-cell TNF receptors. These data demonstrate that DCex can mediate essential innate immune functions that were previously ascribed to DCs.
自分泌和旁分泌细胞通讯可由多种介质介导，包括膜相关蛋白、分泌蛋白和外泌体。外泌体是30 - 100纳米的内体来源囊泡，由被含有跨膜蛋白的脂质双层包围的胞质物质组成。我们之前已经表明，树突状细胞（DCs）在其表面表达多种肿瘤坏死因子超家族配体（TNFSFLs），通过这些配体它们可以诱导肿瘤细胞凋亡死亡以及激活自然杀伤（NK）细胞。在本研究中，我们证明，与DCs类似，DC来源的外泌体（DCex）在其表面表达肿瘤坏死因子（TNF）、Fas配体（FasL）和肿瘤坏死因子相关凋亡诱导配体（TRAIL），通过这些物质它们可以触发肿瘤细胞中的半胱天冬酶激活和凋亡。我们还表明，在DCex肿瘤坏死因子与NK细胞肿瘤坏死因子受体相互作用时，DCex可激活NK细胞并刺激它们分泌干扰素γ（IFNγ）。这些数据表明，DCex可以介导以前归因于DCs的基本固有免疫功能。
