Neutrophil "plucking" on Megakaryocytes Drives Platelet Production and Boosts Cardiovascular Disease

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2022 Oct 22

PMID 36272416

Authors

Tobias Petzold

Zhe Zhang

Ivan Ballesteros

Inas Saleh

Amin Polzin

Manuela Thienel

Lulu Liu

Qurrat Ul Ain

Vincent Ehreiser

Christian Weber

Badr Kilani

Pontus Mertsch

Jeremias Gotschke

Sophie Cremer

Wenwen Fu

Michael Lorenz

Hellen Ishikawa-Ankerhold

Elisabeth Raatz

Shaza El-Nemr

Agnes Gorlach

Esther Marhuenda

Konstantin Stark

Joachim Pircher

David Stegner

Christian Gieger

Marc Schmidt-Supprian

Florian Gaertner

Isaac Almendros

Malte Kelm

Christian Schulz

Andres Hidalgo

Steffen Massberg

Affiliations

Soon will be listed here.

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.

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