Platelets Disseminate Extracellular Vesicles in Lymph in Rheumatoid Arthritis.
Platelets Disseminate Extracellular Vesicles in Lymph in Rheumatoid Arthritis.
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DOI：
10.1161/atvbaha.119.313698
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发表时间：
2020-04
期刊：
影响因子：
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通讯作者：
Boilard É
中科院分区：
文献类型：
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作者：
Tessandier N;Melki I;Cloutier N;Allaeys I;Miszta A;Tan S;Milasan A;Michel S;Benmoussa A;Lévesque T;Côté F;McKenzie SE;Gilbert C;Provost P;Brisson AR;Wolberg AS;Fortin PR;Martel C;Boilard É
淋巴系统是一个循环系统，它单向地将间质组织液引流回血液循环。虽然淋巴被白细胞用于免疫监视，但血小板和红细胞仍然无法接近。活化的细胞释放亚微米细胞外囊泡（EV），其从供体细胞运输分子。在类风湿性关节炎中，EV积聚在关节中，它们可以与许多细胞谱系相互作用。然而，EV是否可以退出发炎组织进行再循环尚不清楚。在这里，我们研究了炎症期间发生的血管渗漏是否有利于EV进入淋巴系统。使用自身免疫性炎性关节炎的体内模型，我们发现，有一个流入的血小板EV，但不是EV从红细胞或白细胞，在联合引流淋巴。与血小板EV相比，淋巴血小板EV缺乏线粒体细胞器，不能促进凝血。淋巴液中血小板EV内流与关节血管渗漏一致，并涉及纤维蛋白原受体α2bβ3和血小板源性5-羟色胺。这些研究结果表明，血小板可以传播他们的EV在流体中是无法接近血小板和超越关节在这种疾病。本文提供了一个在线视觉概述。
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. 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. These findings show that platelets can disseminate their EV in fluid that is inaccessible to platelets and beyond the joint in this disease. An online visual overview is available for this article.