TREM-like transcript 1: a more sensitive marker of platelet activation than P-selectin in humans and mice

Research output: Contribution to journalArticle

Authors

Colleges, School and Institutes

External organisations

  • Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, United Kingdom y.senis@bham.ac.uk.

Abstract

Thrombi can be divided into a core of tightly packed, highly activated P-selectin-positive platelets, and a shell of loosely packed, P-selectin-negative platelets. TREM-like transcript-1 (TLT-1) is an immunoreceptor tyrosine-based inhibition motif (ITIM)-containing receptor that is highly expressed in α-granules of platelets, which gets rapidly upregulated to the surface upon activation. TLT-1 has been proposed to bind fibrinogen and facilitate platelet activation. However, the function of TLT-1 in thrombus formation and stability remains undefined. The aim of this study was to determine the expression of TLT-1 in activated platelets relative to P-selectin during platelet activation and thrombus formation in vivo. We show that activation of both murine and human platelets with thrombin, and the GPVI-specific agonist collagen-related peptide results in a more rapid and greater upregulation of TLT-1 surface expression compared with P-selectin. TLT-1 was also found to more rapidly translocate to the surface of activated platelets compared with P-selectin during laser-induced thrombus formation in mouse cremaster arterioles. TLT-1 expression was detected throughout the entire thrombi whereas P-selectin was only observed in a highly localized region within the thrombus core, directly adjacent to the site of injury, demonstrating for the first time the presence of activated platelets in the thrombus shell.

Details

Original languageEnglish
Pages (from-to)2072-2078
Number of pages7
JournalBlood Advances
Volume2
Issue number16
Publication statusPublished - 28 Aug 2018

Keywords

  • TLT-1, P-selectin, α-granule, platelet activation, thrombus