Platelet CLEC-2: Roles Beyond Hemostasis

Author:

Tsukiji Nagaharu1,Shirai Toshiaki12,Osada Makoto3,Inoue Osamu4,Ozaki Yukio5,Suzuki-Inoue Katsue1

Affiliation:

1. Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan

2. Department of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon

3. School of Medical Technology, Faculty of Health Science, Gunma Paz University, Takasaki, Japan

4. Infection Control Office, Yamanashi University Hospital, Yamanashi, Japan

5. Fuefuki Central Hospital, Fuefuki, Japan

Abstract

AbstractC-type lectin-like receptor 2 (CLEC-2) has been identified on the surface of platelets as a receptor for a platelet activating snake venom, rhodocytin/aggretin. CLEC-2 belongs to a C-type lectin superfamily and binds to a sialoglycoprotein, podoplanin, in vivo. Platelets play a crucial role in hemostasis and thrombosis, but recent studies have uncovered multiple roles of platelets beyond hemostasis in physiology and pathology. The interaction between platelet CLEC-2 and podoplanin is the key to several roles of platelets beyond hemostasis. The spatial and temporal expression patterns of podoplanin regulate vascular/lymphatic development, maintenance of vascular integrity, tissue regeneration, and some pathological processes including tumor metastasis and thromboinflammation. CLEC-2 facilitates blood/lymphatic vessel separation during embryonic development by binding to podoplanin on lymphatic endothelial cells. The leakage of platelets from hyperpermeable vessels for maintaining vascular integrity during inflammation depends on CLEC-2. During wound healing, the expression of podoplanin in keratinocytes is upregulated, which helps in the process. Podoplanin is expressed on the surface of tumor cells and facilitates hematogenous metastasis by inducing platelet aggregation through CLEC-2. During thrombotic processes, such as development of deep vein thrombosis, podoplanin is upregulated on unknown cells in the vessel wall in the area of inflammation, facilitates thrombus formation, and promotes further inflammation by binding to CLEC-2. In this article, the roles of platelets beyond hemostasis are comprehensively reviewed.

Publisher

Georg Thieme Verlag KG

Subject

Cardiology and Cardiovascular Medicine,Hematology

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