Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA.
Int J Mol Sci. 2022 Oct 19;23(20):12513. doi: 10.3390/ijms232012513.
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.
外泌体介导细胞间通讯，在细胞和组织之间传递信息。我们使用来自人类或鼠源、癌细胞或非癌细胞系的 10 个放射性标记的外泌体，探索了外泌体组织隔离是由外泌体还是组织决定的。我们测量了这些外泌体在静脉注射到雄性 CD-1 小鼠后被肝脏、肾脏、脾脏和肺隔离的情况。除了三种外泌体被肾脏隔离外，所有外泌体都被所有组织吸收，但外泌体和组织之间的隔离水平差异很大。来源物种（鼠与人类）或来源（癌细胞与非癌细胞）对外泌体组织隔离没有影响。J774A.1 外泌体被肝脏隔离涉及甘露糖-6-磷酸（M6P）受体。麦胚凝集素（WGA）或脂多糖（LPS）处理增强了脑和肺中外泌体的隔离，但抑制了肝和脾中外泌体的隔离。对 LPS 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脑的结果，并在外泌体和组织之间发现了明显的聚类。总之，我们没有发现证据表明存在控制外泌体-组织相互作用的普遍结合位点。相反，组织对外泌体的隔离受到外泌体和组织的差异调节，WGA 和炎症可能刺激或抑制外泌体的隔离。
