Immunity · 2022
Neutrophil "plucking" on megakaryocytes drives platelet production and boosts cardiovascular disease.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
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
Аннотация
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.