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
