Platelets mediate separation of blood and lymphatic vessels.

摘要

Mammals circulate blood and maintain tissue fluid balance through distinct blood and lymphatic vascular networks. Separation of blood and lymphatic vessels requires the hematopoietic signaling proteins SYK and SLP-76, but how blood cells perform this function is not known. We have used genetic fate-mapping studies to exclude direct hematopoietic cell contribution to vascular endothelium during this process. We find that Podoplanin (PDPN), a cell surface protein expressed by lymphatic but not blood vessel endothelium, is required in a common pathway with SLP-76 for separation of the blood and lymphatic vasculatures. Loss of signaling by CLEC-2, a PDPN receptor known to activate SYK and SLP-76 signaling, confers blood-lymphatic vascular mixing identical to that in animals lacking PDPN, SYK or SLP-76. CLEC-2 is expressed selectively by platelets, and conditional deletion of Slp-76 in platelets reproduces this vascular mixing phenotype. Platelets are activated and form aggregates on lymphatic endothelium during blood flow ex vivo, and at blood-lymphatic separation points in the developing mouse vasculature. These studies reveal a previously unappreciated role for platelets that respond to lymphatic endothelial cells and mediate blood-lymphatic vascular separation during embryonic development.