From the Centre de recherche du CHU de Québec, Canada (N.T., I.M., N.C., I.A., S.M., T.L., C.G., P.P., P.R.F., E.B.).
Département de microbiologie-infectiologie et d'immunologie, Université Laval, QC, Canada (N.T., I.M., N.C., I.A., S.M., T.L., C.G., P.P., P.R.F., E.B.).
Arterioscler Thromb Vasc Biol. 2020 Apr;40(4):929-942. doi: 10.1161/ATVBAHA.119.313698. Epub 2020 Feb 27.
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 α2bβ and platelet-derived serotonin.
These findings show that platelets can disseminate their EV in fluid that is inaccessible to platelets and beyond the joint in this disease.
淋巴系统是一个单向引流间质组织液回流至血液循环的循环系统。虽然淋巴被白细胞用于免疫监视，但它仍然无法被血小板和红细胞利用。激活的细胞会释放出亚微米级别的细胞外囊泡（EV），这些 EV 可以将分子从供体细胞中运输出来。在类风湿关节炎中，EV 会在关节中积累，在那里它们可以与众多细胞谱系相互作用。然而，EV 是否可以离开炎症组织进行再循环尚不清楚。在这里，我们研究了炎症过程中发生的血管渗漏是否有利于 EV 进入淋巴系统。方法和结果：我们使用自身免疫性炎症性关节炎的体内模型表明，在关节引流的淋巴中存在血小板 EV 的涌入，但不存在来自红细胞或白细胞的 EV。与血液血小板 EV 不同，淋巴中的血小板 EV 缺乏线粒体器官，并且不能促进凝血。淋巴中血小板 EV 的涌入与关节血管渗漏一致，并暗示了纤维蛋白原受体 α2bβ 和血小板衍生的 5-羟色胺的作用。结论：这些发现表明，在这种疾病中，血小板可以将其 EV 扩散到血小板无法到达的关节外的液体中。
