Platelet P-selectin triggers rapid surface exposure of tissue factor in monocytes

Abstract

Tissue factor (TF) plays a central role in haemostasis and thrombosis. Following vascular damage, vessel wall TF initiates the extrinsic coagulation cascade. TF can also be exposed by monocytes. Inflammatory or infectious stimuli trigger synthesis of new TF protein by monocytes over the course of hours. It has also been suggested that monocytes can expose TF within minutes when stimulated by activated platelets. Here, we have confirmed that monocytes rapidly expose TF in whole blood and further demonstrate that platelet P-selectin exposure is necessary and sufficient. Monocyte TF exposure increased within five minutes in response to platelet activation by PAR1-AP, PAR4-AP or CRP-XL. PAR1-AP did not trigger TF exposure on isolated monocytes unless platelets were also present. In whole blood, PAR1-AP-triggered TF exposure required P-selectin and PGSL-1. In isolated monocytes, although soluble recombinant P-selectin had no effect, P-selectin coupled to 2 µm beads triggered TF exposure. Cycloheximide did not affect rapid TF exposure, indicating that de novo protein synthesis was not required. These data show that P-selectin on activated platelets rapidly triggers TF exposure on monocytes. This may represent a mechanism by which platelets and monocytes rapidly contribute to intravascular coagulation.

Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19

“…TF expression was maximal at 2 hours of interaction, indicating that platelet-induced TF expression is a Platelets from patients with COVID-19 induce monocyte TF expression through mechanisms depending on P-selectin and integrin a IIb /b 3 P-selectin and integrin a IIb /b 3 play major roles in platelet-leukocyte interaction and platelet-mediated reprogramming of leukocyte responses, including monocyte TF expression. 14,16,23,24,45 To better understand the molecular mechanisms underlying platelet-induced TF expression by monocytes in COVID-19, we performed ex vivo platelet-monocyte coculture for 2 hours in the presence of an anti-P-selectin neutralizing antibody or the clinically approved antia IIb /b 3 monoclonal antibody abciximab. As shown in Figure 6B, both anti-P-selectin and abciximab were able to prevent platelets from COVID-19 patients to induce TF expression in monocytes.…”

Interrelations Between Growth Differentiation Factor 15, P-Selectin and Galectin-3 and Clinical Course in Patients With Arterial Hypertension and Type 2 Diabetes Mellitus

“…We also revealed a significant increase of P-selectin levels in patients with grade 3 hypertension. It is known that P-selectin, which is released on activated platelets and endothelial cells, can act as a counter ligand for GPIbα and, therefore, may mediate platelet adhesion and thrombus formation [15,16]. We suggest that the increase of P-selectin level reflects the activation of the platelet link of systemic inflammation in patients with grade 3 hypertension.…”

Impact of Epicatechin on the Procoagulant Activities of Microparticles

“…The epicatechin-induced decrease in GpIb-positive microparticles could impair their reactivity to thrombin and von Willebrand factor [ 46 ], and might have a direct impact on myocardial infarction pathogenesis [ 47 ]. Furthermore, epicatechin effect from 1 µM on P-selectin-expressing PMPs could have a beneficial effect on the risk of major adverse cardiovascular events after myocardial infarction [ 48 , 49 ], probably because of P-selectin role in thrombosis and in the recruitment of leukocytes in inflammation [ 50 , 51 ].…”