Jackson C W, Hutson N K, Steward S A, Ashmun R A, Davis D S, Edwards H H, Rehg J E, Dockter M E
Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN.
Blood. 1988 Jun;71(6):1676-86.
The mechanisms that determine and regulate platelet size are unknown. By phase microscopy, we observed that Wistar Furth (WF) rats had macrothrombocytopenia. In this study, we have characterized and compared platelets and megakaryocytes of WF rats with those of Wistar, Long-Evans hooded (LE), and Sprague-Dawley rats. In addition, we have examined the mode of inheritance of this WF rat platelet abnormality. The average platelet count of WF rats was only one-third that of the other three rat strains. In contrast, the mean platelet volume (MPV) of adult WF rats was twice that of the other rat strains; however, the average megakaryocyte diameter and DNA content distribution of WF rats were not significantly different from those of LE rats. The average megakaryocyte concentration was 30% lower in the WF strain compared with that of LE rats. Mazelike membrane formations were observed in WF platelets and megakaryocytes by electron microscopy. Reciprocal crosses of WF and LE rats resulted in offspring with MPVs and platelet counts like those of LE rats, indicating that the macrothrombocytopenic trait is recessive in its inheritance. Reciprocal marrow transplants between the WF and LE strains resulted in MPVs like those of the donor strain, demonstrating that the macrothrombocytopenia is an intrinsic marrow abnormality of the WF strain. Splenectomy did not alter the MPV of WF rats. The response of WF megakaryocytes and platelets to severe, acute thrombocytopenia was similar to that of LE rats except that the shift to higher megakaryocyte DNA contents was muted and platelet recovery was slower in the WF rats. In summary, the WF rat has a hereditary macrothrombocytopenia that is recessive in nature and not due to differences in megakaryocyte size or DNA content. These results suggest that the macrothrombocytopenia of WF rats results from the formation of fewer platelets per megakaryocyte, possibly resulting from a qualitative or quantitative defect in some component necessary for proper subdivision of megakaryocyte cytoplasm into platelets.
决定和调节血小板大小的机制尚不清楚。通过相差显微镜观察，我们发现Wistar Furth（WF）大鼠存在大血小板减少症。在本研究中，我们对WF大鼠的血小板和巨核细胞与Wistar、Long-Evans hooded（LE）和Sprague-Dawley大鼠的血小板和巨核细胞进行了特征描述和比较。此外，我们还研究了这种WF大鼠血小板异常的遗传方式。WF大鼠的平均血小板计数仅为其他三种大鼠品系的三分之一。相比之下，成年WF大鼠的平均血小板体积（MPV）是其他大鼠品系的两倍；然而，WF大鼠的平均巨核细胞直径和DNA含量分布与LE大鼠并无显著差异。与LE大鼠相比，WF品系的平均巨核细胞浓度低30%。通过电子显微镜观察，在WF大鼠的血小板和巨核细胞中发现了迷宫样的膜结构。WF大鼠和LE大鼠的正反交后代的MPV和血小板计数与LE大鼠相似，这表明大血小板减少性状在遗传上是隐性的。WF品系和LE品系之间的相互骨髓移植导致的MPV与供体品系相似，这表明大血小板减少症是WF品系内在的骨髓异常。脾切除术并未改变WF大鼠的MPV。WF大鼠的巨核细胞和血小板对严重急性血小板减少的反应与LE大鼠相似，只是向更高巨核细胞DNA含量的转变不明显，且WF大鼠的血小板恢复较慢。总之，WF大鼠存在遗传性大血小板减少症，其本质是隐性的，并非由于巨核细胞大小或DNA含量的差异。这些结果表明，WF大鼠的大血小板减少症是由于每个巨核细胞产生的血小板数量减少所致，这可能是由于巨核细胞细胞质正确细分形成血小板所需的某些成分存在质量或数量缺陷。
