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首页> 外文期刊>Leukemia >Caspase activation is involved in early megakaryocyte differentiation but not in platelet production from megakaryocytes
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Caspase activation is involved in early megakaryocyte differentiation but not in platelet production from megakaryocytes

机译：Caspase活化涉及早期的巨核细胞分化，但不含巨核细胞的血小板生产

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To elucidate whether caspase activation is involved in megakaryopoiesis, we characterized megakaryocytes (MKs) in vav-bcl-2 transgenic (Tg) mice, in which Bcl-2 is overexpressed in hematopoietic cells. To exclude the effect of splenomegaly in Tg mice on megakaryopoiesis, splenectomy was performed. After splenectomy, basal platelet counts in peripheral blood were not significantly different between Tg and wild-type (WT) mice. However, when experimental thrombocytopenia was induced by injecting 5-fluorouracil into splenectomized mice, overshoot of platelet counts during the recovery phase was hardly observed in Tg mice. Analyses of MK ploidy during the recovery phase showed that MKs less than 16N ploidy were significantly decreased in Tg mice, suggesting that MK supply from progenitors is impaired. Supporting this, differentiation of CD34-/c-kit+/Sca-1+/Lineage- stem cells into MKs was significantly hampered in Tg mice, whereas megakaryocyte-erythroid progenitors (MEPs) normally differentiated into MKs. It suggests that differentiation into MKs is impaired in Tg mice before the stage of MEP. Furthermore, MK colony formation in WT cells was dose-dependently inhibited in the presence of a caspase inhibitor. Contrary, Bcl-2-overexpressing MKs showed normal ability for in vitro platelet production. We thus believe that caspase activation is involved in the differentiation of progenitors into megakaryocytic lineage but not in platelet production.
机译：为了阐明Caspase活化是否参与巨孔孔，我们在VAV-BCL-2转基因（Tg）小鼠中表征了巨核细胞（MKS），其中Bcl-2在造血细胞中过表达。为了排除脾肿大在Tg小鼠对Megakaryopoiesis的影响，进行了脾切除。在脾切除术后，TG和野生型（WT）小鼠之间的外周血中的基础血小板计数没有显着差异。然而，当通过将5-氟尿嘧啶注入脾切除的小鼠诱导实验血小板减少时，在Tg小鼠中几乎不观察到在回收阶段期间的血小板计数的过冲。在恢复期期间的MK倍性分析显示，TG小鼠的MKS小于16N倍增性显着降低，表明祖细胞的MK供应受损。支持这一点，CD34- / c-kit + / SCA-1 /谱系干细胞在TG小鼠中分化为MKS，而Megakaryocyte-eryThroid祖（MEPS）通常与MKS分化为MKS。它表明，在MEP的阶段之前，在TG小鼠中将分化为MKS。此外，在胱天蛋白酶抑制剂存在下剂量依赖性抑制WT细胞中的MK菌落形成。相反，Bcl-2过表达MKS显示出体外血小板生产的正常能力。因此，我们认为Caspase活化涉及祖细胞分化成巨核细胞谱系，但不在血小板生产中。

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