Cargando…

IL-1α induces thrombopoiesis through megakaryocyte rupture in response to acute platelet needs

Intravital visualization of thrombopoiesis revealed that formation of proplatelets, which are cytoplasmic protrusions in bone marrow megakaryocytes (MKs), is dominant in the steady state. However, it was unclear whether this is the only path to platelet biogenesis. We have identified an alternative...

Descripción completa

Detalles Bibliográficos
Autores principales: Nishimura, Satoshi, Nagasaki, Mika, Kunishima, Shinji, Sawaguchi, Akira, Sakata, Asuka, Sakaguchi, Hiroyasu, Ohmori, Tsukasa, Manabe, Ichiro, Italiano, Joseph E., Ryu, Tomiko, Takayama, Naoya, Komuro, Issei, Kadowaki, Takashi, Eto, Koji, Nagai, Ryozo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427781/
https://www.ncbi.nlm.nih.gov/pubmed/25963822
http://dx.doi.org/10.1083/jcb.201410052
_version_ 1782370781281386496
author Nishimura, Satoshi
Nagasaki, Mika
Kunishima, Shinji
Sawaguchi, Akira
Sakata, Asuka
Sakaguchi, Hiroyasu
Ohmori, Tsukasa
Manabe, Ichiro
Italiano, Joseph E.
Ryu, Tomiko
Takayama, Naoya
Komuro, Issei
Kadowaki, Takashi
Eto, Koji
Nagai, Ryozo
author_facet Nishimura, Satoshi
Nagasaki, Mika
Kunishima, Shinji
Sawaguchi, Akira
Sakata, Asuka
Sakaguchi, Hiroyasu
Ohmori, Tsukasa
Manabe, Ichiro
Italiano, Joseph E.
Ryu, Tomiko
Takayama, Naoya
Komuro, Issei
Kadowaki, Takashi
Eto, Koji
Nagai, Ryozo
author_sort Nishimura, Satoshi
collection PubMed
description Intravital visualization of thrombopoiesis revealed that formation of proplatelets, which are cytoplasmic protrusions in bone marrow megakaryocytes (MKs), is dominant in the steady state. However, it was unclear whether this is the only path to platelet biogenesis. We have identified an alternative MK rupture, which entails rapid cytoplasmic fragmentation and release of much larger numbers of platelets, primarily into blood vessels, which is morphologically and temporally different than typical FasL-induced apoptosis. Serum levels of the inflammatory cytokine IL-1α were acutely elevated after platelet loss or administration of an inflammatory stimulus to mice, whereas the MK-regulator thrombopoietin (TPO) was not elevated. Moreover, IL-1α administration rapidly induced MK rupture–dependent thrombopoiesis and increased platelet counts. IL-1α–IL-1R1 signaling activated caspase-3, which reduced plasma membrane stability and appeared to inhibit regulated tubulin expression and proplatelet formation, and ultimately led to MK rupture. Collectively, it appears the balance between TPO and IL-1α determines the MK cellular programming for thrombopoiesis in response to acute and chronic platelet needs.
format Online
Article
Text
id pubmed-4427781
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-44277812015-11-11 IL-1α induces thrombopoiesis through megakaryocyte rupture in response to acute platelet needs Nishimura, Satoshi Nagasaki, Mika Kunishima, Shinji Sawaguchi, Akira Sakata, Asuka Sakaguchi, Hiroyasu Ohmori, Tsukasa Manabe, Ichiro Italiano, Joseph E. Ryu, Tomiko Takayama, Naoya Komuro, Issei Kadowaki, Takashi Eto, Koji Nagai, Ryozo J Cell Biol Research Articles Intravital visualization of thrombopoiesis revealed that formation of proplatelets, which are cytoplasmic protrusions in bone marrow megakaryocytes (MKs), is dominant in the steady state. However, it was unclear whether this is the only path to platelet biogenesis. We have identified an alternative MK rupture, which entails rapid cytoplasmic fragmentation and release of much larger numbers of platelets, primarily into blood vessels, which is morphologically and temporally different than typical FasL-induced apoptosis. Serum levels of the inflammatory cytokine IL-1α were acutely elevated after platelet loss or administration of an inflammatory stimulus to mice, whereas the MK-regulator thrombopoietin (TPO) was not elevated. Moreover, IL-1α administration rapidly induced MK rupture–dependent thrombopoiesis and increased platelet counts. IL-1α–IL-1R1 signaling activated caspase-3, which reduced plasma membrane stability and appeared to inhibit regulated tubulin expression and proplatelet formation, and ultimately led to MK rupture. Collectively, it appears the balance between TPO and IL-1α determines the MK cellular programming for thrombopoiesis in response to acute and chronic platelet needs. The Rockefeller University Press 2015-05-11 /pmc/articles/PMC4427781/ /pubmed/25963822 http://dx.doi.org/10.1083/jcb.201410052 Text en © 2015 Nishimura et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Nishimura, Satoshi
Nagasaki, Mika
Kunishima, Shinji
Sawaguchi, Akira
Sakata, Asuka
Sakaguchi, Hiroyasu
Ohmori, Tsukasa
Manabe, Ichiro
Italiano, Joseph E.
Ryu, Tomiko
Takayama, Naoya
Komuro, Issei
Kadowaki, Takashi
Eto, Koji
Nagai, Ryozo
IL-1α induces thrombopoiesis through megakaryocyte rupture in response to acute platelet needs
title IL-1α induces thrombopoiesis through megakaryocyte rupture in response to acute platelet needs
title_full IL-1α induces thrombopoiesis through megakaryocyte rupture in response to acute platelet needs
title_fullStr IL-1α induces thrombopoiesis through megakaryocyte rupture in response to acute platelet needs
title_full_unstemmed IL-1α induces thrombopoiesis through megakaryocyte rupture in response to acute platelet needs
title_short IL-1α induces thrombopoiesis through megakaryocyte rupture in response to acute platelet needs
title_sort il-1α induces thrombopoiesis through megakaryocyte rupture in response to acute platelet needs
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427781/
https://www.ncbi.nlm.nih.gov/pubmed/25963822
http://dx.doi.org/10.1083/jcb.201410052
work_keys_str_mv AT nishimurasatoshi il1ainducesthrombopoiesisthroughmegakaryocyteruptureinresponsetoacuteplateletneeds
AT nagasakimika il1ainducesthrombopoiesisthroughmegakaryocyteruptureinresponsetoacuteplateletneeds
AT kunishimashinji il1ainducesthrombopoiesisthroughmegakaryocyteruptureinresponsetoacuteplateletneeds
AT sawaguchiakira il1ainducesthrombopoiesisthroughmegakaryocyteruptureinresponsetoacuteplateletneeds
AT sakataasuka il1ainducesthrombopoiesisthroughmegakaryocyteruptureinresponsetoacuteplateletneeds
AT sakaguchihiroyasu il1ainducesthrombopoiesisthroughmegakaryocyteruptureinresponsetoacuteplateletneeds
AT ohmoritsukasa il1ainducesthrombopoiesisthroughmegakaryocyteruptureinresponsetoacuteplateletneeds
AT manabeichiro il1ainducesthrombopoiesisthroughmegakaryocyteruptureinresponsetoacuteplateletneeds
AT italianojosephe il1ainducesthrombopoiesisthroughmegakaryocyteruptureinresponsetoacuteplateletneeds
AT ryutomiko il1ainducesthrombopoiesisthroughmegakaryocyteruptureinresponsetoacuteplateletneeds
AT takayamanaoya il1ainducesthrombopoiesisthroughmegakaryocyteruptureinresponsetoacuteplateletneeds
AT komuroissei il1ainducesthrombopoiesisthroughmegakaryocyteruptureinresponsetoacuteplateletneeds
AT kadowakitakashi il1ainducesthrombopoiesisthroughmegakaryocyteruptureinresponsetoacuteplateletneeds
AT etokoji il1ainducesthrombopoiesisthroughmegakaryocyteruptureinresponsetoacuteplateletneeds
AT nagairyozo il1ainducesthrombopoiesisthroughmegakaryocyteruptureinresponsetoacuteplateletneeds