Insights Into Immunothrombosis: The Interplay Among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13.

Junxian Yang,Jiangguo Lin,Tiantian Hong,Quan Long,Zhiwei Wu,Wang Liu,Jiaqi Huang

doi:10.3389/fimmu.2020.610696

Abstract

Both neutrophil extracellular traps (NETs) and von Willebrand factor (VWF) are essential for thrombosis and inflammation. During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. The adhesive activity of VWF multimers is regulated by a specific metalloprotease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Increasing evidence indicates that the interaction between NETs and VWF contributes to arterial and venous thrombosis as well as inflammation. Furthermore, contents released from activated neutrophils or NETs induce the reduction of ADAMTS13 activity, which may occur in both thrombotic microangiopathies (TMAs) and acute ischemic stroke (AIS). Recently, NET is considered as a driver of endothelial damage and immunothrombosis in COVID-19. In addition, the levels of VWF and ADAMTS13 can predict the mortality of COVID-19. In this review, we summarize the biological characteristics and interactions of NETs, VWF, and ADAMTS13, and discuss their roles in TMAs, AIS, and COVID-19. Targeting the NET-VWF axis may be a novel therapeutic strategy for inflammation-associated TMAs, AIS, and COVID-19.

Highlights

Neutrophils, the most abundant leukocyte subset in circulation, act as the critical responders during innate immunity and inflammation [1]
Pathways and mechanisms of neutrophil extracellular traps (NETs) formation are diverse and sophisticated upon different stimuli, they all come to an identical outcome: histone degradation, chromatin decondensation, and NETs released from neutrophils [41]
Most of the literature mainly focuses on which stimuli can induce NET formation and which proteins can inhibit the process

Summary

Frontiers in Immunology

Received: 27 September 2020 Accepted: 02 November 2020 Published: 02 December 2020. Citation: Yang J, Wu Z, Long Q, Huang J, Hong T, Liu W and Lin J (2020) Insights Into Immunothrombosis: The. Received: 27 September 2020 Accepted: 02 November 2020 Published: 02 December 2020 Both neutrophil extracellular traps (NETs) and von Willebrand factor (VWF) are essential for thrombosis and inflammation. During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. Contents released from activated neutrophils or NETs induce the reduction of ADAMTS13 activity, which may occur in both thrombotic microangiopathies (TMAs) and acute ischemic stroke (AIS). We summarize the biological characteristics and interactions of NETs, VWF, and ADAMTS13, and discuss their roles in TMAs, AIS, and COVID-19. Targeting the NET-VWF axis may be a novel therapeutic strategy for inflammationassociated TMAs, AIS, and COVID-19

INTRODUCTION

NET Structure and Components

Mechanisms of NET Formation

The Glycoprotein von Willebrand Factor

CONCLUSIONS