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Semin Thromb Hemost 2018; 44(02): 126-134
DOI: 10.1055/s-0037-1604090
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Platelet CLEC-2: Roles Beyond Hemostasis

Katsue Suzuki-Inoue
1   Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
,
Nagaharu Tsukiji
1   Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
,
Toshiaki Shirai
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
,
Makoto Osada
3   School of Medical Technology, Faculty of Health Science, Gunma Paz University, Takasaki, Japan
,
Osamu Inoue
4   Infection Control Office, Yamanashi University Hospital, Yamanashi, Japan
,
Yukio Ozaki
5   Fuefuki Central Hospital, Fuefuki, Japan
› Author Affiliations
Further Information

Publication History

Publication Date:
09 October 2017 (online)

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Abstract

C-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.

Keywords

platelets - CLEC-2 - podoplanin - blood/lymphatic vessel development - thromboinflammation
 

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