Journal Article 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

209 ( 3 )  , pp.453 - 466 , 2015-05-11 , Rockefeller University Press
生体顕微鏡観察により新たな血小板産生過程を明らかに -インターロイキン1アルファにより誘導される巨核球破裂型造血- . 京都大学プレスリリース. 2015-05-18.
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.

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