OBJECTIVE The lymphatic system is a circulatory system that unidirectionally drains the interstitial tissue fluid back to blood circulation. Although lymph is utilized by leukocytes for immune surveillance, it remains inaccessible to platelets and erythrocytes. Activated cells release submicron extracellular vesicles (EV) that transport molecules from the donor cell. In rheumatoid arthritis, EV accumulate in the joint where they can interact with numerous cellular lineages. However, whether EV can exit the inflamed tissue to recirculate is unknown. Here, we investigated whether vascular leakage that occurs during inflammation could favor EV access to the lymphatic system. Approach and Results: Using an in vivo model of autoimmune inflammatory arthritis, we show that there is an influx of platelet EV, but not EV from erythrocytes or leukocytes, in joint-draining lymph. In contrast to blood platelet EV, lymph platelet EV lacked mitochondrial organelles and failed to promote coagulation. Platelet EV influx in lymph was consistent with joint vascular leakage and implicated the fibrinogen receptor α2bβ3 and platelet-derived serotonin. CONCLUSIONS These findings show that platelets can disseminate their EV in fluid that is inaccessible to platelets and beyond the joint in this disease.

中文翻译：

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血小板在类风湿关节炎的淋巴中传播细胞外囊泡。

目的淋巴系统是一种循环系统，可单向将间质组织液排回血液循环。尽管白细胞利用淋巴来进行免疫监视，但血小板和红细胞仍无法获得淋巴。活化的细胞释放出亚微米的细胞外小泡（EV），该小泡从供体细胞转运分子。在类风湿关节炎中，EV积聚在关节中，在那里它们可以与众多细胞谱系相互作用。但是，EV是否可以离开发炎组织进行再循环尚不清楚。在这里，我们调查了炎症过程中发生的血管渗漏是否有助于电动汽车进入淋巴系统。方法和结果：使用自身免疫性炎性关节炎的体内模型，我们发现有血小板EV流入，但不是红细胞或白细胞的EV流入，在关节引流淋巴中。与血小板EV相反，淋巴血小板EV缺乏线粒体细胞器并且不能促进凝血。淋巴中的血小板EV流入与关节血管渗漏一致，并牵涉到纤维蛋白原受体α2bβ3和血小板衍生的血清素。结论这些发现表明，在这种疾病中，血小板可以将其EV散布到血小板无法进入的液体中和关节之外。