Thrombo-Inflammation: A Focus on NTPDase1/CD39.

Silvana Morello,Elisabetta Caiazzo,Roberta Turiello,Carla Cicala

doi:10.3390/cells10092223

Silvana Morello, Elisabetta Caiazzo + Show 2 more

Open Access

https://doi.org/10.3390/cells10092223

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Journal: Cells	Publication Date: Aug 27, 2021
Citations: 15	License type: CC BY 4.0

Affiliation: University of Naples Federico II, University of Salerno

Abstract

There is increasing evidence for a link between inflammation and thrombosis. Following tissue injury, vascular endothelium becomes activated, losing its antithrombotic properties whereas inflammatory mediators build up a prothrombotic environment. Platelets are the first elements to be activated following endothelial damage; they participate in physiological haemostasis, but also in inflammatory and thrombotic events occurring in an injured tissue. While physiological haemostasis develops rapidly to prevent excessive blood loss in the endothelium activated by inflammation, hypoxia or by altered blood flow, thrombosis develops slowly. Activated platelets release the content of their granules, including ATP and ADP released from their dense granules. Ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1)/CD39 dephosphorylates ATP to ADP and to AMP, which in turn, is hydrolysed to adenosine by ecto-5′-nucleotidase (CD73). NTPDase1/CD39 has emerged has an important molecule in the vasculature and on platelet surfaces; it limits thrombotic events and contributes to maintain the antithrombotic properties of endothelium. The aim of the present review is to provide an overview of platelets as cellular elements interfacing haemostasis and inflammation, with a particular focus on the emerging role of NTPDase1/CD39 in controlling both processes.

Highlights

Experimental and clinical data demonstrate that inflammation may cause haemostatic aberration, leading to thrombosis
Platelets play a central role in haemostasis, thrombosis, and atherosclerosis; they are crucial in the primary haemostatic defence mechanism through adhesion to damaged vessels and the following activation
P-selectin (CD62P), normally stored in α granules, translocates onto platelet surfaces and engages its receptor P-selectin glycoprotein-1 (PSGL-1) on polymorphonuclear leukocytes (PMNs) and monocytes; the interaction of platelets with leukocytes may result in local fibrin deposition through an increased tissue factor (TF) expression in these cells [12,13,14,15] which, in turn, will promote blood coagulation

Summary

Introduction

Experimental and clinical data demonstrate that inflammation may cause haemostatic aberration, leading to thrombosis. The crosstalk between inflammation and thrombosis passes through the interaction among several cells including platelets, monocytes, macrophages, talking to each other and all with endothelial cells. When the endothelium is intact, under physiological conditions, the balance between its pro-and anti-thrombotic features is preserved; on the contrary, when the endothelium is activated, such as during inflammation, it loses these properties and becomes a suitable surface where inflammatory events build up a prothrombotic environment [1,2,4,5]. We highlight the emerging role of NTPDase1/CD39 in the crosstalk between inflammation and thrombosis. NTPDase1/CD39 is an ectonucleotidase hydrolysing ATP to ADP and AMP; it is highly expressed on vasculature, platelets, and immune cells and is able to control thrombotic and immune processes within an inflammatory environment [6,7,8]

Platelet Activation

Nucleotides and Signaling

Further Perspectives

Conclusions