Platelets mediate lymphovenous hemostasis to maintain blood-lymphatic separation throughout life
Paul R. Hess, … , Lijun Xia, Mark L. Kahn
Paul R. Hess, … , Lijun Xia, Mark L. Kahn
Published December 2, 2013
Citation Information: J Clin Invest. 2014;124(1):273-284. https://doi.org/10.1172/JCI70422.
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Platelets mediate lymphovenous hemostasis to maintain blood-lymphatic separation throughout life

Abstract

Mammals transport blood through a high-pressure, closed vascular network and lymph through a low-pressure, open vascular network. These vascular networks connect at the lymphovenous (LV) junction, where lymph drains into blood and an LV valve (LVV) prevents backflow of blood into lymphatic vessels. Here we describe an essential role for platelets in preventing blood from entering the lymphatic system at the LV junction. Loss of CLEC2, a receptor that activates platelets in response to lymphatic endothelial cells, resulted in backfilling of the lymphatic network with blood from the thoracic duct (TD) in both neonatal and mature mice. Fibrin-containing platelet thrombi were observed at the LVV and in the terminal TD in wild-type mice, but not Clec2-deficient mice. Analysis of mice lacking LVVs or lymphatic valves revealed that platelet-mediated thrombus formation limits LV backflow under conditions of impaired valve function. Examination of mice lacking integrin-mediated platelet aggregation indicated that platelet aggregation stabilizes thrombi that form in the lymphatic vascular environment to prevent retrograde blood flow. Collectively, these studies unveil a newly recognized form of hemostasis that functions with the LVV to safeguard the lymphatic vascular network throughout life.

Authors

Paul R. Hess, David R. Rawnsley, Zoltán Jakus, Yiqing Yang, Daniel T. Sweet, Jianxin Fu, Brett Herzog, MinMin Lu, Bernhard Nieswandt, Guillermo Oliver, Taija Makinen, Lijun Xia, Mark L. Kahn

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Figure 5

Large platelet thrombi are observed throughout the TD of Prox1+/– and Itga9–/– animals.

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Large platelet thrombi are observed throughout the TD of Prox1+/– and It...
(A) Representative LVVs and lymphatic valves in Prox1+/– and Itga9–/– mice, which had impaired valve development. Valve rudiments are labeled and/or denoted by arrows. (B) Platelet-containing thrombi were observed in the TD adjacent to the SV in E17.5 Prox1+/– embryos. (C) Platelet-containing thrombi were observed next to the LVV and in the TD adjacent to the SV in E17.5 Itga9–/– embryos. (D) Platelet-containing thrombi extended to the proximal TD in the chest of E17.5 Prox1+/– and Itga9–/– embryos. Dotted outlines denote vessel walls. Scale bars: 50 μm.