Marked improvement of thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura by pegylated recombinant human megakaryocyte growth and development factor

Kazunori Shibuya, Tomoaki Kuwaki, Emiko Tahara, Chizuru Yuki, Hiromichi Akahori, Takashi Kato, Hiroshi Miyazaki

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective. We examined the stimulatory effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production in male (NZW × BXSB) Fl (W/B F1) mice, a murine model of idiopathic thrombocytopenic purpura. Materials and Methods. A cohort of 19- to 25-week-old, severely thrombocytopenic male W/B F1 mice were given PEG-rHuMGDF at different dosing schedules. Before and at various times after therapy, platelet counts, reticulated platelets, platelet lifespan, and levels of platelet-associated immunoglobulin G were measured. Analysis of megakaryocytic cells was performed. Results. Treatment of male W/B F1 mice with PEG-rHuMGDF (30 μg/kg/day) three times per week for several weeks resulted in sustained thrombocytosis, accompanied by increased megakaryocytopoiesis in both the bone marrow and spleen. The degree of the platelet response to PEG-rHuMGDF varied between individual mice, likely reflecting the heterogeneity of the disease. Production of new platelets in response to PEG-rHuMGDF was manifested by an increase in reticulated platelets. Levels of platelet-associated immunoglobulin G decreased inversely during periods of thrombocytosis. PEG-rHuMGDF therapy also improved thrombocytopenia in male W/B F1 mice refractory to splenectomy. Platelet lifespan was not affected by PEG-rHuMGDF. Male W/B F1 mice treated with pegylated murine MGDF, a homologue of PEG-rHuMGDF, had persistent thrombocytosis for at least 7 months, suggesting that antiplatelet antibody production was not enhanced. Conclusion. PEG-rHuMGDF therapy potently stimulated platelet production, effectively ameliorating thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura.

Original languageEnglish
Pages (from-to)1185-1192
Number of pages8
JournalExperimental Hematology
Volume30
Issue number10
DOIs
Publication statusPublished - 2002 Oct 1
Externally publishedYes

Fingerprint

Idiopathic Thrombocytopenic Purpura
Thrombocytopenia
Blood Platelets
Thrombocytosis
Immunoglobulin G
polyethylene glycol-recombinant human megakaryocyte growth and development factor
Thrombopoiesis
Splenectomy
Platelet Count
Antibody Formation
Appointments and Schedules
Therapeutics
Spleen
Bone Marrow

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Marked improvement of thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura by pegylated recombinant human megakaryocyte growth and development factor. / Shibuya, Kazunori; Kuwaki, Tomoaki; Tahara, Emiko; Yuki, Chizuru; Akahori, Hiromichi; Kato, Takashi; Miyazaki, Hiroshi.

In: Experimental Hematology, Vol. 30, No. 10, 01.10.2002, p. 1185-1192.

Research output: Contribution to journalArticle

Shibuya, Kazunori ; Kuwaki, Tomoaki ; Tahara, Emiko ; Yuki, Chizuru ; Akahori, Hiromichi ; Kato, Takashi ; Miyazaki, Hiroshi. / Marked improvement of thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura by pegylated recombinant human megakaryocyte growth and development factor. In: Experimental Hematology. 2002 ; Vol. 30, No. 10. pp. 1185-1192.
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T1 - Marked improvement of thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura by pegylated recombinant human megakaryocyte growth and development factor

AU - Shibuya, Kazunori

AU - Kuwaki, Tomoaki

AU - Tahara, Emiko

AU - Yuki, Chizuru

AU - Akahori, Hiromichi

AU - Kato, Takashi

AU - Miyazaki, Hiroshi

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N2 - Objective. We examined the stimulatory effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production in male (NZW × BXSB) Fl (W/B F1) mice, a murine model of idiopathic thrombocytopenic purpura. Materials and Methods. A cohort of 19- to 25-week-old, severely thrombocytopenic male W/B F1 mice were given PEG-rHuMGDF at different dosing schedules. Before and at various times after therapy, platelet counts, reticulated platelets, platelet lifespan, and levels of platelet-associated immunoglobulin G were measured. Analysis of megakaryocytic cells was performed. Results. Treatment of male W/B F1 mice with PEG-rHuMGDF (30 μg/kg/day) three times per week for several weeks resulted in sustained thrombocytosis, accompanied by increased megakaryocytopoiesis in both the bone marrow and spleen. The degree of the platelet response to PEG-rHuMGDF varied between individual mice, likely reflecting the heterogeneity of the disease. Production of new platelets in response to PEG-rHuMGDF was manifested by an increase in reticulated platelets. Levels of platelet-associated immunoglobulin G decreased inversely during periods of thrombocytosis. PEG-rHuMGDF therapy also improved thrombocytopenia in male W/B F1 mice refractory to splenectomy. Platelet lifespan was not affected by PEG-rHuMGDF. Male W/B F1 mice treated with pegylated murine MGDF, a homologue of PEG-rHuMGDF, had persistent thrombocytosis for at least 7 months, suggesting that antiplatelet antibody production was not enhanced. Conclusion. PEG-rHuMGDF therapy potently stimulated platelet production, effectively ameliorating thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura.

AB - Objective. We examined the stimulatory effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production in male (NZW × BXSB) Fl (W/B F1) mice, a murine model of idiopathic thrombocytopenic purpura. Materials and Methods. A cohort of 19- to 25-week-old, severely thrombocytopenic male W/B F1 mice were given PEG-rHuMGDF at different dosing schedules. Before and at various times after therapy, platelet counts, reticulated platelets, platelet lifespan, and levels of platelet-associated immunoglobulin G were measured. Analysis of megakaryocytic cells was performed. Results. Treatment of male W/B F1 mice with PEG-rHuMGDF (30 μg/kg/day) three times per week for several weeks resulted in sustained thrombocytosis, accompanied by increased megakaryocytopoiesis in both the bone marrow and spleen. The degree of the platelet response to PEG-rHuMGDF varied between individual mice, likely reflecting the heterogeneity of the disease. Production of new platelets in response to PEG-rHuMGDF was manifested by an increase in reticulated platelets. Levels of platelet-associated immunoglobulin G decreased inversely during periods of thrombocytosis. PEG-rHuMGDF therapy also improved thrombocytopenia in male W/B F1 mice refractory to splenectomy. Platelet lifespan was not affected by PEG-rHuMGDF. Male W/B F1 mice treated with pegylated murine MGDF, a homologue of PEG-rHuMGDF, had persistent thrombocytosis for at least 7 months, suggesting that antiplatelet antibody production was not enhanced. Conclusion. PEG-rHuMGDF therapy potently stimulated platelet production, effectively ameliorating thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura.

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