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Titolo:
Platelets exposed to elevated levels of endogenous thrombopoietin in vivo have a reduced response to megakaryocyte growth and development factor in vitro
Autore:
Nishiyama, U; Morita, H; Torii, Y; Kuwaki, T; Shimizu, E; Akahori, H; Kato, T; Miyazaki, H;
Indirizzi:
Kirin Brewery Co Ltd, Pharmaceut Dev Lab, Gunma 3701295, Japan Kirin Brewery Co Ltd Gunma Japan 3701295 t Dev Lab, Gunma 3701295, Japan Kirin Brewery Co Ltd, Pharmaceut Res Lab, Gunma, Japan Kirin Brewery Co Ltd Gunma Japan Ltd, Pharmaceut Res Lab, Gunma, Japan
Titolo Testata:
THROMBOSIS AND HAEMOSTASIS
fascicolo: 1, volume: 85, anno: 2001,
pagine: 152 - 159
SICI:
0340-6245(200101)85:1<152:PETELO>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
C-MPL LIGAND; RECOMBINANT HUMAN THROMBOPOIETIN; ACTIVATION IN-VITRO; CHEMOTHERAPY-INDUCED THROMBOCYTOPENIA; HUMAN BLOOD-PLATELETS; TYROSINE-PHOSPHORYLATION; NONHUMAN-PRIMATES; MYELOSUPPRESSED MICE; PROGENITOR CELLS; ABSENT RADII;
Keywords:
thrombopoietin; megakaryocyte growth and development factor; platelet; aggregation; c-Mpl;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Miyazaki, H Kirin Brewery Co Ltd, Pharmaceut Dev Lab, 3 Miyahara Cho, Gunma 3701295, Japan Kirin Brewery Co Ltd 3 Miyahara Cho Gunma Japan 3701295 Japan
Citazione:
U. Nishiyama et al., "Platelets exposed to elevated levels of endogenous thrombopoietin in vivo have a reduced response to megakaryocyte growth and development factor in vitro", THROMB HAEM, 85(1), 2001, pp. 152-159

Abstract

Thrombopoietin (TPO), or megakaryocyte growth and development factor (MGDF), has been shown to potentiate the sensitivity of normal human platelets to various agonists in vitro. The present study investigated the functional and biochemical properties of platelets from mice rendered thrombocytopenicby sublethal irradiation with regard to the reactivity to recombinant murine MGDF (rmMGDF) in vitro. During the course of reversible thrombocytopeniafollowing irradiation, platelets from irradiated mice which had lower platelet counts and reciprocally higher plasma TPO levels showed lower reactivity to rmMGDF in agonist-induced platelet aggregation. Intravenous injections of recombinant soluble murine c-Mpl (sMpl), which has the ability to capture TPO, after irradiation restored the reactivity of platelets at the platelet nadir to rmMGDF. On the other hand, platelets prepared from normal mice 3 h after a single intravenous injection of pegylated rmMGDF did not respond to rmMGDF. There was a marked decrease in c-Mpl and Janus kinase 2 (JAK2) in platelets from irradiated mice at the platelet nadir. Similar resultswere observed with platelets from mice administered pegylated rmMGDF. JAK2was only moderately decreased, however, in platelets from mice given sMpl after irradiation. These results indicate that exposure of platelets to increased endogenous TPO levels in vivo in thrombocytopenic mice leads to a reduction in the platelet reactivity to rmMGDF in vitro. Further, these results suggest that the c-Mpl-mediated signaling pathway, which is essential for the priming effect of rmMGDF, is defective in thrombocytopenic murine platelets.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 18:54:17