title: [A role of the platelet receptor CLEC-2 in lymphangiogenesis and its clinical application].
abstract: Platelets play a pivotal role in thrombosis and hemostasis; however, a series of recent research has demonstrated that platelets also play roles other than in clotting. We discovered that a platelet receptor, C-type lectin-like receptor 2 (CLEC-2), facilitates lymph/blood vessel separation in the developmental stage by binding to its ligand, podoplanin, on lymphatic endothelial cells. We have previously reported that CLEC-2-deficient mice showed blood-filled lymphatic vessels and severe edema, suggesting that CLEC-2 is essential for lymph/blood vessel separation; however, its mechanism has not been elucidated to date. Although CLEC-2 is mainly expressed in platelets and megakaryocytes, marginal expression is observed in other blood cells in mice. We found that specific deletion of CLEC-2 from platelets/megakaryocytes also impaired blood/lymphatic vessel separation, suggesting that CLEC-2 in platelets is required for separation. Based on several in vitro experiments, we proposed the mechanism of blood/lymphatic vessel separation as follows: In the developmental stage, when lymphatic vessels separate from cardinal veins, CLEC-2 in platelets binds to podoplanin in lymphatic endothelial cells. Subsequent platelet activation results in the release of platelet granule contents, including the transforming growth factor 8 family. These platelet contents inhibit migration, proliferation, and tube formation of lymphatic endothelial cells, which facilitates blood/lymphatic vessel separation. We also found that soluble CLEC-2 is released upon platelet activation. We hypothesized that plasma soluble CLEC-2 could be a marker of thrombosis and established an ELISA system to measure soluble CLEC-2. Although current tests for in vivo platelet activation require special methods for blood sampling, soluble CLEC-2 can be measured with ordinary blood sampling. We are now investigating the potential of soluble CLEC-2 as a useful marker for in vivo platelet activation.
authors.affiliation: Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Chuo 409-3898, Japan. mosada@yamanashi.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Osada
authors.forename: Katsue
authors.initials: K
authors.lastname: Suzuki-Inoue
authors.forename: Osamu
authors.initials: O
authors.lastname: Inoue
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ozaki
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000378:metabolism*; D015539:Platelet Activation / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D037181:Lectins, C-Type