Thromb Haemost 2019; 119(08): 1274-1282
DOI: 10.1055/s-0039-1692983
Theme Issue Article
Georg Thieme Verlag KG Stuttgart · New York

Platelet–Neutrophil Crosstalk in Atherothrombosis

Joachim Pircher
1  Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig Maximilian University of Munich, Munich, Germany
2  German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
,
Bernd Engelmann
3  Institut für Laboratoriumsmedizin, Klinikum der Universität München, Ludwig Maximilian University of Munich, Munich, Germany
,
Steffen Massberg
1  Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig Maximilian University of Munich, Munich, Germany
2  German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
,
Christian Schulz
1  Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig Maximilian University of Munich, Munich, Germany
2  German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
› Author Affiliations
Funding This work was supported by the Deutsche Forschungsgemeinschaft (SFB 1123 project A07 to C.S. and project B06 to S.M. and B.E.) and the DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance (to C.S. and S.M.). J.P. is supported by a Gerok position of the SFB 914.
Further Information

Publication History

14 February 2019

03 June 2019

Publication Date:
29 June 2019 (eFirst)

Abstract

Atherothrombosis is a frequent cause of cardiovascular mortality. It is mostly triggered by plaque rupture and exposure of the thrombogenic subendothelial matrix, which initiates platelet aggregation and clot formation. Current antithrombotic strategies, however, target both thrombosis and physiological hemostasis and thereby increase bleeding risk. Thus, there is an unmet clinical need for optimized therapies. Neutrophil activation and consecutive interactions of neutrophils and platelets contribute mechanistically to thromboinflammation and arterial thrombosis, and thus present a potential therapeutic target. Platelet–neutrophil interactions are mediated through adhesion molecules such as P-selectin and P-selectin glycoprotein ligand 1 as well as glycoprotein Ib and macrophage-1 antigen, which mediate physical cell interactions and intracellular signaling. Release of soluble mediators as well as direct signaling between platelets and neutrophils lead to their reciprocal activation and neutrophil release of extracellular traps, scaffolds of condensed chromatin that play a prothrombotic role in atherothrombosis. In this article, we review the role of neutrophils and neutrophil-derived prothrombotic molecules in platelet activation and atherothrombosis, and highlight potential therapeutic targets.