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Platelet immunoreceptor tyrosine‐based activation motif ( ITAM ) and hem ITAM signaling and vascular integrity in inflammation and development
Author(s) -
Lee R. H.,
Bergmeier W.
Publication year - 2016
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.13250
Subject(s) - gpvi , syk , microbiology and biotechnology , platelet , receptor , platelet activation , inflammation , signal transduction , immunology , biology , chemistry , cancer research , tyrosine kinase , biochemistry
Summary Platelets are essential for maintaining hemostasis following mechanical injury to the vasculature. Besides this established function, novel roles of platelets are becoming increasingly recognized, which are critical in non‐injury settings to maintain vascular barrier integrity. For example, during embryogenesis platelets act to support the proper separation of blood and lymphatic vessels. This role continues beyond birth, where platelets prevent leakage of blood into the lymphatic vessel network. During the course of inflammation, platelets are necessary to prevent local hemorrhage due to neutrophil diapedesis and disruption of endothelial cell‐cell junctions. Surprisingly, platelets also work to secure tumor‐associated blood vessels, inhibiting excessive vessel permeability and intra‐tumor hemorrhaging. Interestingly, many of these novel platelet functions depend on immunoreceptor tyrosine‐based activation motif ( ITAM ) signaling but not on signaling via G protein‐coupled receptors, which plays a crucial role in platelet plug formation at sites of mechanical injury. Murine platelets express two ITAM ‐containing receptors: the Fc receptor γ‐chain (FcRγ), which functionally associates with the collagen receptor GPVI , and the C‐type lectin‐like 2 ( CLEC ‐2) receptor, a hem ITAM receptor for the mucin‐type glycoprotein podoplanin. Human platelets express an additional ITAM receptor, Fcγ RIIA . These receptors share common downstream effectors, including Syk, SLP ‐76 and PLC γ2. Here we will review the recent literature that highlights a critical role for platelet GPVI /FcRγ and CLEC ‐2 in vascular integrity during development and inflammation in mice and discuss the relevance to human disease.