Neutrophil 'plucking' on megakaryocytes drives platelet production and boosts cardiovascular disease

Autor: Tobias Petzold, Zhe Zhang, Iván Ballesteros, Inas Saleh, Amin Polzin, Manuela Thienel, Lulu Liu, Qurrat Ul Ain, Vincent Ehreiser, Christian Weber, Badr Kilani, Pontus Mertsch, Jeremias Götschke, Sophie Cremer, Wenwen Fu, Michael Lorenz, Hellen Ishikawa-Ankerhold, Elisabeth Raatz, Shaza El-Nemr, Agnes Görlach, Esther Marhuenda, Konstantin Stark, Joachim Pircher, David Stegner, Christian Gieger, Marc Schmidt-Supprian, Florian Gaertner, Isaac Almendros, Malte Kelm, Christian Schulz, Andrés Hidalgo, Steffen Massberg
Rok vydání: 2022
Předmět:
Zdroj: Immunity
Immunity 55, 2285-2299.e7 (2022)
ISSN: 1097-4180
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: