Ebbe S, Maurer H
Lawrence Berkeley Laboratory, CA.
Exp Hematol. 1994 Sep;22(10):1011-5.
The concept that megakaryocytopoiesis is regulated in part by the number of megakaryocytes themselves, separately from its regulation by the number of platelets, is referred to as autoregulation. Its occurrence has been implied from animal models that demonstrate compensated megakaryocytopenia. In that condition, normal platelet production can occur even though numbers of megakaryocytes are substantially reduced, and individual megakaryocytes exhibit changes consistent with their being stimulated. The present experiments were undertaken to determine whether the converse situation, namely suppression of megakaryocytopoiesis by an excess of megakaryocytes, could be created. The experimental model consisted of C57Bl mice in which as many as 10 isogeneic femurs were implanted subcutaneously 10 weeks before analysis. The implanted femurs contained hematopoietic marrow morphologically. They incorporated radioiron, but only about 40% as much as an equal number of normal femurs, so hematopoiesis did not regenerate to the full potential of the implanted marrows. After implantation of nine or 10 femurs, thrombocytopoiesis was normal as judged by platelet counts, mean platelet volumes, numbers of megakaryocytes in tibial marrow, and megakaryocyte sizes. Hematocrits were increased, but plasma erythropoietin levels were normal. The implants showed a 15- to 20-hour incorporation of radioiron of 9.4 +/- 0.5%. Iron incorporation into endogenous bones and spleen was reduced, demonstrating that erythropoiesis was redistributed. The total incorporation of iron into all hematopoietic tissue was slightly increased, but red-cell iron incorporation was normal, implying that there was more ineffective erythropoiesis than normal. Leukocyte counts, differentials, and tibial cellularity were normal. After implantation of three or six femurs, no abnormalities of hematopoiesis were detected, even though the implants incorporated iron in proportion to their number. Thus, erythropoiesis was adjusted by the excess of total marrow caused by nine or 10 subcutaneously implanted femurs. This is about the maximum of implanted marrow that is feasible with this model, and the failure to observe suppression of megakaryocytopoiesis may have been due to an inability to achieve a large enough number of megakaryocytes to elicit a detectable response. Alternatively, autoregulation of megakaryocytes may depend more on the marrow concentration of megakaryocytes than on the total body content.
巨核细胞生成部分受巨核细胞自身数量调节，与血小板数量调节无关，这一概念被称为自动调节。动物模型显示代偿性巨核细胞减少，提示了自动调节的存在。在这种情况下，即使巨核细胞数量大幅减少，正常的血小板生成仍可发生，且单个巨核细胞表现出受刺激的变化。本实验旨在确定相反的情况是否会发生，即巨核细胞过多是否会抑制巨核细胞生成。实验模型由C57Bl小鼠组成，在分析前10周皮下植入多达10根同基因股骨。植入的股骨含有形态学上的造血骨髓。它们能摄取放射性铁，但摄取量仅为同等数量正常股骨的约40%，因此造血功能无法完全恢复到植入骨髓的潜力。植入9根或10根股骨后，根据血小板计数、平均血小板体积、胫骨骨髓中巨核细胞数量和巨核细胞大小判断，血小板生成正常。血细胞比容升高，但血浆促红细胞生成素水平正常。植入物显示放射性铁的摄取率为9.4±0.5%，持续15至20小时。内源性骨骼和脾脏中铁的摄取减少，表明红细胞生成重新分布。所有造血组织中铁的总摄取量略有增加，但红细胞中铁的摄取正常，这意味着无效红细胞生成比正常情况更多。白细胞计数、分类和胫骨细胞数量正常。植入3根或6根股骨后，未检测到造血异常，尽管植入物按比例摄取铁。因此，9根或10根皮下植入股骨导致的骨髓总量过多调节了红细胞生成。这是该模型可行的植入骨髓的最大量，未观察到巨核细胞生成受抑制可能是由于无法获得足够数量的巨核细胞以引发可检测的反应。或者，巨核细胞自动调节可能更多地取决于骨髓中巨核细胞的浓度，而非全身含量。
