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*

*この研究の対応する著者

研究成果: Article査読

3 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1185-1192
ページ数8
ジャーナルExperimental Hematology
30
10
DOI
出版ステータスPublished - 2002 10 1
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 血液学
  • 遺伝学
  • 細胞生物学
  • 癌研究

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