Regulation of thrombopoiesis: effects of the degree of thrombocytopenia on megakaryocyte ploidy and platelet volume.
Regulation of thrombopoiesis: effects of the degree of thrombocytopenia on megakaryocyte ploidy and platelet volume.
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DOI：
10.1182/blood.v70.1.177.bloodjournal701177
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发表时间：
1987-07
期刊：
影响因子：
20.3
通讯作者：
L. Corash;H. Y. Chen;J. Levin;G. Baker;H. Lu;Y. Mok
中科院分区：
文献类型：
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作者：
L. Corash;H. Y. Chen;J. Levin;G. Baker;H. Lu;Y. Mok
我们已经建立了一种小鼠模型和技术，用来连续研究实验性免疫性血小板减少症诱导后的血小板生成。骨髓巨核细胞倍体分布采用多克隆巨核细胞特异性探针和双色荧光激活的流式细胞术进行检测。结果表明，正常小鼠骨髓巨核细胞倍性类型为16N。诱导急性重度血小板减少(血小板计数<0.05×10(6)微L)后，骨髓巨核细胞倍性的系列研究显示，在出现血小板减少的12、24和36小时后，其倍性分布没有明显变化。48h时，染色体倍性类型由16N变为32N，64N类型显著增加(P<.001)。在出现血小板减少的120小时后，倍体分布恢复正常。较轻程度的血小板减少(血小板计数降至0.100~0.200×10(6)/微L)可延迟模式倍体类型从16N向32N的转变，直到出现血小板减少后72小时。慢性严重的血小板减少症(血小板计数连续7天低于0.05×10(6)/微升)导致模式倍体类型在血小板减少阶段从16N转变为32N，在恢复期增加64N巨核细胞类型。在诱导血小板减少后，同时测量分离的总血小板群体的平均血小板体积(MPV)。MPV显著升高(P<0.001)，早在急性、重度血小板减少发作后8小时，在倍体分布转变前40小时。轻度血小板减少(血小板计数降至0.400×10(6)/微升)与倍体改变无关，但确实导致平均血小板体积显著增加(P<0.001)。这些研究表明，血小板减少对巨核细胞倍性分布的影响的时间关系和大小取决于血小板减少刺激的程度和持续时间，而实验性血小板减少对血小板体积和巨核细胞倍性的影响是分离的。
We have established a murine model and techniques with which to serially study thrombocytopoiesis after induction of experimental immune thrombocytopenia of variable severity and duration. Bone marrow megakaryocyte ploidy distribution was determined by using unfractionated bone marrow, a polyclonal megakaryocyte-specific probe, and two-color, fluorescence-activated flow cytometry. With these techniques, the modal megakaryocyte ploidy class in normal murine bone marrow was 16N. Serial studies of bone marrow megakaryocyte ploidy after the induction of acute, severe thrombocytopenia (platelet count, less than 0.05 X 10(6) microL) demonstrated no detectable change in the ploidy distribution at 12, 24, and 36 hours after the onset of thrombocytopenia. At 48 hours, the modal ploidy class shifted from 16N to 32N, and the 64N class increased significantly (P less than .001). The ploidy distribution returned to normal 120 hours after the onset of thrombocytopenia. A lesser degree of thrombocytopenia (platelet count reduction to 0.100 to 0.200 X 10(6)/microL) delayed the modal ploidy class shift from 16N to 32N until 72 hours after the onset of thrombocytopenia. Chronic, severe thrombocytopenia (platelet count, less than 0.05 X 10(6)/microL for seven days) resulted in a modal ploidy class shift from 16N to 32N during the thrombocytopenic phase and an enhanced increase in the 64N megakaryocyte class during the recovery phase. Mean platelet volume (MPV) was simultaneously measured on isolated total platelet populations after induction of thrombocytopenia. MPV was significantly increased (P less than .001) as early as eight hours after the onset of acute, severe thrombocytopenia, 40 hours before a shift in the ploidy distribution. Mild thrombocytopenia (platelet count reduction to 0.400 X 10(6)/microL) was not associated with a ploidy shift but did result in a significantly increased MPV (P less than .001). These studies demonstrate that the temporal relationship and magnitude of the effects of thrombocytopenia upon megakaryocyte ploidy distribution are dependent upon the degree and the duration of the thrombocytopenic stimulus and that the effects of experimental thrombocytopenia on platelet volume and megakaryocyte ploidy are dissociated.