Kuter D J, Beeler D L, Rosenberg R D
Hematology Unit, Massaschusetts General Hospital, Boston.
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11104-8. doi: 10.1073/pnas.91.23.11104.
The circulating blood platelet is produced by the bone marrow megakaryocyte. In response to a decrease in the platelet count, megakaryocytes increase in number and ploidy. Although this feedback loop has long been thought to be mediated by a circulating hematopoietic factor, no such factor has been purified. Using a model of thrombocytopenia in sheep, we have identified an active substance called megapoietin, which stimulated an increase in the number and ploidy of megakaryocytes in bone marrow culture. Circulating levels of this factor could be quantified with this assay and were found to be inversely proportional to the platelet count of the sheep. Levels increased from < 0.26 pM in normal sheep to 25-40 pM in thrombocytopenic sheep. From large amounts of thrombocytopenic sheep plasma we have purified a 31,200-Da protein and found that it retained the ability to stimulate both megakaryocyte number and ploidy in vitro. Injection of partially purified megapoietin into rats stimulated a 24% increase in megakaryocyte number and a 60% increase in mean ploidy as well as a 77% increase in the platelet count. Sheep platelets bound megapoietin and the amount of platelets required to eliminate half the activity in vitro was close to the amount associated with this same level of activity in vivo. We believe that megapoietin is the physiologically relevant mediator of megakaryocyte growth and platelet production. Moreover, our data suggest that the level of megapoietin is directly determined by the ability of platelets to remove megapoietin from the circulation.
循环血液中的血小板由骨髓巨核细胞产生。为应对血小板计数的下降，巨核细胞的数量和倍性会增加。尽管长期以来人们一直认为这种反馈回路是由一种循环造血因子介导的，但尚未纯化出这样的因子。利用绵羊血小板减少症模型，我们鉴定出一种名为巨核细胞生成素的活性物质，它能刺激骨髓培养物中巨核细胞数量和倍性的增加。这种因子的循环水平可以通过该测定法进行量化，并且发现与绵羊的血小板计数成反比。水平从正常绵羊的<0.26 pM增加到血小板减少症绵羊的25 - 40 pM。我们从大量血小板减少症绵羊血浆中纯化出一种31,200道尔顿的蛋白质，并发现它在体外仍保留刺激巨核细胞数量和倍性的能力。将部分纯化的巨核细胞生成素注射到大鼠体内可刺激巨核细胞数量增加24%，平均倍性增加60%，血小板计数增加77%。绵羊血小板结合巨核细胞生成素，体外消除一半活性所需的血小板量与体内相同活性水平相关的量接近。我们认为巨核细胞生成素是巨核细胞生长和血小板产生的生理相关介质。此外，我们的数据表明，巨核细胞生成素的水平直接由血小板从循环中清除巨核细胞生成素的能力决定。
