1. Platelet–Neutrophil Crosstalk in Atherothrombosis
- Author
-
Bernd Engelmann, Christian Schulz, Joachim Pircher, and Steffen Massberg
- Subjects
Blood Platelets ,0301 basic medicine ,Platelet Aggregation ,Neutrophils ,Inflammation ,Cell Communication ,030204 cardiovascular system & hematology ,Extracellular Traps ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Adhesion ,medicine ,Animals ,Humans ,Platelet ,Platelet activation ,Cell adhesion ,Hemostasis ,Membrane Glycoproteins ,biology ,Chemistry ,Cell adhesion molecule ,Thrombosis ,Hematology ,Atherosclerosis ,Platelet Activation ,P-Selectin ,Treatment Outcome ,030104 developmental biology ,Glycoprotein Ib ,Cancer research ,biology.protein ,medicine.symptom ,Signal transduction ,Signal Transduction - 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.
- Published
- 2019