Characteristics of Exosomes and the Vascular Landscape Regulate Exosome Sequestration by Peripheral Tissues and Brain.

Characteristics of Exosomes and the Vascular Landscape Regulate Exosome Sequestration by Peripheral Tissues and Brain.
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DOI:
10.3390/ijms232012513
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发表时间:
2022-10-19
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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--
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外切体介导胞间通讯,在细胞和组织之间传递信息。我们探索了外切体组织隔离是由外切体决定的,还是使用来自人类或小鼠、癌症或非肿瘤细胞系的10个放射性标记外切体的组织决定的。静脉注射到雄性CD-1小鼠体内后,我们测量了这些外切体在肝、肾、脾和肺中的隔离情况。除了3个外切体的肾脏隔离外,所有的外切体都被所有组织所结合,但外切体和组织之间的隔离水平差异很大。来源的种类(小鼠与人类)或来源(癌细胞与非癌细胞)不影响组织隔离。肝脏对J774A.1外切体的截留涉及甘露糖-6-磷酸(M6P)受体。小麦胚凝集素(WGA)或脂多糖(LPS)处理促进了外切体在脑和肺的封存,但抑制了肝和脾的封存。对脂多糖的反应不能预测对WGA的反应。路径和热图分析包括我们发表的关于大脑的结果,并发现外体和组织之间存在明显的集群。总而言之,我们没有发现控制外体-组织相互作用的通用结合部位的证据。相反,组织对外切体的隔离受到外切体和组织的不同调控,并可能受到WGA和炎症的刺激或抑制。
Exosomes mediate intercellular communication, shuttling messages between cells and tissues. We explored whether exosome tissue sequestration is determined by the exosomes or the tissues using ten radiolabeled exosomes from human or murine, cancerous or noncancerous cell lines. We measured sequestration of these exosomes by the liver, kidney, spleen, and lung after intravenous injection into male CD-1 mice. Except for kidney sequestration of three exosomes, all exosomes were incorporated by all tissues, but sequestration levels varied greatly among exosomes and tissues. Species of origin (mouse vs. human) or source (cancerous vs. noncancerous cells) did not influence tissue sequestration. Sequestration of J774A.1 exosomes by liver involved the mannose-6 phosphate (M6P) receptor. Wheatgerm agglutinin (WGA) or lipopolysaccharide (LPS) treatments enhanced sequestration of exosomes by brain and lung but inhibited sequestration by liver and spleen. Response to LPS was not predictive of response to WGA. Path and heat map analyses included our published results for brain and found distinct clusters among the exosomes and the tissues. In conclusion, we found no evidence for a universal binding site controlling exosome-tissue interactions. Instead, sequestration of exosomes by tissues is differentially regulated by both exosomes and tissues and may be stimulated or inhibited by WGA and inflammation.
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