1. Neutrophil "plucking" on megakaryocytes drives platelet production and boosts cardiovascular disease.
- Author
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Petzold, Tobias, Zhang, Zhe, Ballesteros, Iván, Saleh, Inas, Polzin, Amin, Thienel, Manuela, Liu, Lulu, Ul Ain, Qurrat, Ehreiser, Vincent, Weber, Christian, Kilani, Badr, Mertsch, Pontus, Götschke, Jeremias, Cremer, Sophie, Fu, Wenwen, Lorenz, Michael, Ishikawa-Ankerhold, Hellen, Raatz, Elisabeth, El-Nemr, Shaza, and Görlach, Agnes
- Subjects
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MEGAKARYOCYTES , *MYOSIN light chain kinase , *BLOOD platelets , *MYOCARDIAL infarction , *NEUTROPHILS , *BONE marrow - Abstract
Intravascular neutrophils and platelets collaborate in maintaining host integrity, but their interaction can also trigger thrombotic complications. We report here that cooperation between neutrophil and platelet lineages extends to the earliest stages of platelet formation by megakaryocytes in the bone marrow. Using intravital microscopy, we show that neutrophils "plucked" intravascular megakaryocyte extensions, termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent migration towards perisinusoidal megakaryocytes, plucking neutrophils actively pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated kinase activation through reactive oxygen species. By these mechanisms, neutrophils accelerate proplatelet growth and facilitate continuous release of platelets in steady state. Following myocardial infarction, plucking neutrophils drove excessive release of young, reticulated platelets and boosted the risk of recurrent ischemia. Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent thrombosis after myocardial infarction and thrombus burden in venous thrombosis. We establish neutrophil plucking as a target to reduce thromboischemic events. • Plucking of neutrophils on megakaryocyte extensions drives platelet production • Neutrophils induce mechanosignaling in megakaryocytes via CXCR4 and NOX2 • Neutrophil plucking boosts thrombus burden in thromboinflammatory diseases The importance of megakaryocyte and neutrophil interactions within the bone marrow is insufficiently understood. Petzold and colleagues define neutrophil "plucking"-induced mechanosignaling in megakaryocytes as a regulator of platelet production that boosts cardiovascular diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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