TGF-β plays a role in platelet-mediated lymph-blood partitioning

In the vascular system, lymphatic vessels play a cooperative role with blood vessels, but they form networks separated from each other. It has been shown that lymph-blood partitioning requires lymphatic endothelial cell (LEC)-induced platelet activation. However, it remains unclear whether platelet activation is involved in establishing a network of lymphatic vessels unconnected to blood vessels. In this study, we show that platelet activation blocks misconnection of lymphatic to blood vessels in peripheral tissues. Angiography detected lymph-blood misconnection in phospholipase Cγ2-deficient mice which lack LEC-induced platelet activation. LEC protrusion was detected inside the blood vessel lumen which can potentially activate platelets. LEC protrusion was immediately retracted by platelet-derived factors containing TGF-β in culture. Inhibition of TGF-β signaling induces the formation of lymph-blood misconnection in mouse embryonic dorsal skin. Our findings advance understanding of peripheral lymph-blood partitioning.