Study on the regulation mechanism of megakaryocyte and thrombo-cytopoiesis

巨核细胞与血小板生成调控机制研究

• 批准号: 61570586
• 负责人: KIMURA Hideo
• 金额: $ 1.41万
• 依托单位: Fukushima Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570586/
• 关键词: Megakaryocytopoiesis; Thrombocytopoiesis; Essential thrombocythemia; GM-CSF; IL-6; トロンボポエチン; CFU-meg; meg-CSA; Megakaryocyropoiesis; 各種造血因子; 巨核球・血小板産生; 巨核球コロニー刺激因子; CFU-Meg; Percoll連続密度勾配; 原発性血小板血症

Megakaryocytopoiesis in essential thrombocythemia (ET) and polycythemia vera (PV)To characterize abnormal megakaryocytopoiesis and thrombopoiesis in ET and PV, bone marrow megakaryocytic progenitors (CFU-MK) were cultured in a methylcellulose system containg human plasma. Most of the ET patients and about two-thirds of the PV patients studied revealed spontaneous CFU-MK colony growth in the absence of stimulator (PHA-LCM). The number of CFU-MK in ET and PV was significantly increased than that of the control subjects. CFU-MK from ET and PV gave rise to larger number of megakaryocytes per each colony compared to the control subjects. Among PV pateints, those who showed spontaneous CFU-MK were associated with an increased megakaryocyte number number on marrow biopsy specimen and thrombocytosis. Patients with reactive thrombocytosis showed no spontaneous CFU-MK growth, similar to the contro subjects. The data suggested that the abnormally incresed number of megakaryocytes and resultant th … More rombocytosis is, at least partly, due to such abnormal CFU-MK population (spontaneous CFU-MK; autonomous or highly sensitive population to the stimulator). Reactive thrombocytosis may be due to some stimuli on post-CFU-MK compartment (possibly due to incresed thrombopoietin).Efect of various pure growth factors on murine megakaryocytopoiesisThe effects of erythropoietin and IL-3 on murine megakaryocytopoiesis in vitro have been previously demonstrated. This time, we studied the effect of GM-CSF (mouse recombinant) on murine megakaryocytopoiesis in vitro and in vivo. The effect of IL-6 (human, recombinant) was also studied.GM-CSF stimulated CFU-MK as well as CFU-GM colony formation in serum depletedagar culture. GM-CSF also increased the size of megakaryocytes and acetylcholinesterase activity of megakarocytes in liquid culture. The effect was found direct using a single megakaryocyte cylture with or without GM-CSF. When injected in vivo (1 ug twice a day, each mouse, for 6 days), two fold increase of granuloctes was observed. CFU-MK numbers in bone marrow and platelet level were not changed.Using the same culture systems, UL-6 was found to promote the maturation but not proliferation of murine megakaryocytes. The effect was direct. The in vivo role of IL-6 remains to be studied. Less

原发性血小板增多症(ET)和真性红细胞增多症(PV)的巨核细胞生成为研究ET和PV中异常的巨核细胞生成和血小板生成，骨髓巨核祖细胞(CFU-MK)在含人血浆的甲基纤维素体系中培养。大多数ET患者和约三分之二的PV患者在没有刺激物的情况下表现出自发的CFU-MK集落生长(PHA-LCM)。ET组和PV组CFU-MK数明显高于对照组。ET和PV的CFU-MK每个集落的巨核细胞数均高于对照组。在PV患者中，那些显示自发CFU-MK的患者与骨髓活检标本中巨核细胞数量增加和血小板增多有关。与对照组相似，反应性血小板增多症患者未见自发的CFU-MK生长。数据表明，巨核细胞数量的异常增加和由此产生的TH…更多的红细胞增多症，至少部分是由于这种异常的CFU-MK群体(自发的CFU-MK；对刺激物高度敏感的自主群体)。反应性血小板增多可能是由于CFU-MK后的某些刺激(可能是由于血小板生成素的增加)。各种纯生长因子对小鼠巨核细胞生成的影响已被证明在体外促红细胞生成素和IL-3对小鼠巨核细胞生成的影响。这一次，我们研究了GM-CSF(小鼠重组)在体内外对小鼠巨核细胞生成的影响。同时观察重组人IL-6对CFU-MK和CFU-GM集落的影响。GM-CSF还能增加液体培养巨核细胞的大小和乙酰胆碱酯酶活性。无论是否加入GM-CSF，直接使用单个巨核细胞培养都能发现这种效应。在体内注射(每天2次，每次1微克，连续6天)，小鼠的粒细胞数增加2倍。在相同的培养条件下，UL-6能促进小鼠巨核细胞的成熟，但不能促进巨核细胞的增殖。其影响是直接的。IL-6在体内的作用还有待研究。较少

项目成果

大越透、木村秀夫 他: 日本血液学会雑誌. 51. 606-611 (1988)

Toru Okoshi、Hideo Kimura 等：日本血液学会杂志 51. 606-611 (1988)。

木村秀夫 他: 医学のあゆみ. 142. 501-502 (1987)

Hideo Kimura 等人：医学史。142. 501-502 (1987)

Kimura H: Acta Haematologica Jpn. 49. 1696-1704 (1986)

木村 H：日本血液学学报。

志賀隆,木村秀夫,他: 日本血液学会誌. (1987)

Takashi Shiga、Hideo Kimura 等人：日本血液学会杂志 (1987)。

Kimura H.: Acta Haematologica Jpn. 49. 1696-1704 (1986)

Kimura H.：日本血液学学报。