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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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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 |
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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 |
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