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

213Citations
Citations of this article
197Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

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.

Cite

CITATION STYLE

APA

Nishimura, S., Nagasaki, M., Kunishima, S., Sawaguchi, A., Sakata, A., Sakaguchi, H., … Nagai, R. (2015). IL-1α induces thrombopoiesis through megakaryocyte rupture in response to acute platelet needs. Journal of Cell Biology, 209(3), 453–466. https://doi.org/10.1083/jcb.201410052

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free