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

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.