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.
View: Text | PDF
Research Article Hematology Article has an altmetric score of 12

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

×

Figure 7

Maintenance of blood-lymphatic separation by LVV function and LV hemostasis.

Options: View larger image (or click on image) Download as PowerPoint
Maintenance of blood-lymphatic separation by LVV function and LV hemosta...
Examination of wild-type and mutant animals revealed the roles of the LVV and CLEC2-mediated LV hemostasis. Left: In healthy wild-type animals, LV hemostasis appears to function intermittently to block the retrograde movement of blood that enters the TD, despite normal LVV function. Middle: Impaired valve function, due either to abnormal LVV formation in Prox1+/– animals or to abnormal lymphatic valve formation in Itga9–/– animals, results in more extensive LV hemostasis that prevents backfilling of the lymphatic network with blood. Right: Loss of platelet CLEC2 function results in backfilling of the lymphatic network with blood despite normal LVV function, while loss of platelet aggregation results in a blood-filled TD despite the formation of platelet thrombi.