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Petzold, T.* ; Zhang, Z.* ; Ballesteros, I.* ; Saleh, I.* ; Polzin, A.* ; Thienel, M.* ; Liu, L.* ; Ul Ain, Q.* ; Ehreiser, V.* ; Weber, C.* ; Kilani, B.* ; Mertsch, P.* ; Götschke, J.* ; Cremer, S.* ; Fu, W.* ; Lorenz, M.* ; Ishikawa-Ankerhold, H.* ; Raatz, E.* ; El-Nemr, S.* ; Görlach, A.* ; Marhuenda, E.* ; Stark, K.* ; Pircher, J.* ; Stegner, D.* ; Gieger, C. ; Schmidt-Supprian, M.* ; Gaertner, F.C.* ; Almendros, I.* ; Kelm, M.* ; Schulz, C.* ; Hidalgo, A.* ; Massberg, S.*

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

Immunity 55, 2285-2299.e7 (2022)

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	Open Access Gold (Paid Option)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Bone Marrow ; Mechanotransduction ; Neutrophils ; Thromboinflammation ; Thrombopoiesis ; Thrombosis; Genetik, DZHK, DZD

ISSN (print) / ISBN 1074-7613

e-ISSN 1097-4180

Journal Immunity

Quellenangaben Volume: 55, Issue: 12, Pages: 2285-2299.e7

Publisher Cell Press

Publishing Place Cambridge, Mass.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)

Grants LMU Munich's Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative
German Centre for Cardiovascular Research (DZHK)
European Research Council (ERC) under the European Union
European Union
German Research Foundation
Leducq Foundation
MICINN
Pro CNIC Foundation
Severo Ochoa Center of Excellence
Forschungskommission of the Medical Faculty of the Heinrich-Heine-Universitat Dusseldorf
Helmholtz Alliance Aging and Metabolic Programming, AMPro
German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD)
Bavarian State Ministry of Health and Care
Fundacion La Caixa
European Research Council (ERC)
Marie Curie Actions (MSCA)
Ministerio de Ciencia e Innovacion (MICINN)