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

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 b...

Full description

Saved in:
Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Vol. 55; no. 12; p. 2285
Main Authors: 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, Görlach, Agnes, Marhuenda, Esther, Stark, Konstantin, Pircher, Joachim, Stegner, David, Gieger, Christian, Schmidt-Supprian, Marc, Gaertner, Florian, Almendros, Isaac, Kelm, Malte, Schulz, Christian, Hidalgo, Andrés, Massberg, Steffen
Format: Journal Article
Language:English
Published: United States 13.12.2022
Subjects:
Blood Platelets - physiology
Cardiovascular Diseases
Humans
Megakaryocytes
Myocardial Infarction
Neutrophils
Thrombopoiesis
Thrombosis
thromboinflammation
thrombosis
neutrophils
thrombopoiesis
mechanotransduction
bone marrow
ISSN:1097-4180, 1097-4180
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1097-4180
1097-4180
DOI:10.1016/j.immuni.2022.10.001