Udupa K B, Lipschitz D A
Blood. 1982 Jun;59(6):1267-71.
The regulation of erythropoiesis is primarily controlled by erythropoietin (Ep). Recently, however, other factors that both stimulate and inhibit erythropoiesis have been reported. Using an in vitro liquid culture of bone marrow cells, a factor in normal mouse serum was demonstrated that markedly stimulated heme synthesis by marrow erythroid cells. In this study, the role of this heme synthesis stimulating factor (HSF) and Ep in the erythropoietic suppression caused by endotoxin administration to mice was examined. Although HSF levels did not alter appreciably after endotoxin injection, marrow erythroid cells from these animals became unresponsive to the factor. This could be reversed if Ep was added to the culture in vitro or if the hormone was injected into the mice 18 hr prior to harvesting the marrow. This marrow erythroid cell response is identical to that seen in animals in whom Ep levels are markedly reduced, such as that found in exhypoxic polycythemia, and suggest a decrease in the hormone following endotoxin administration. Additional studies demonstrated that when Ep was injected into mice 6 hr after endotoxin administration, an increase in femoral erythroid colony-forming units (CFU-E), proerythroblast number, and 59 Fe incorporation into femoral marrow cells could be demonstrated. These findings, together with the marrow erythroid cell response to the hormone, suggest that the mechanism for suppression of erythropoiesis after endotoxin injection is a reduction in the level of circulating Ep.
红细胞生成的调节主要受促红细胞生成素（Ep）控制。然而，最近有报道称，还有其他一些因素既能刺激也能抑制红细胞生成。利用骨髓细胞的体外液体培养，在正常小鼠血清中发现了一种能显著刺激骨髓红系细胞血红素合成的因子。在本研究中，检测了这种血红素合成刺激因子（HSF）和Ep在给小鼠注射内毒素所致红细胞生成抑制中的作用。尽管注射内毒素后HSF水平没有明显改变，但这些动物的骨髓红系细胞对该因子变得无反应。如果在体外培养中加入Ep，或者在采集骨髓前18小时给小鼠注射该激素，这种情况可以逆转。这种骨髓红系细胞反应与Ep水平显著降低的动物（如低氧性红细胞增多症动物）中所见的反应相同，提示内毒素注射后该激素水平下降。进一步的研究表明，在内毒素注射6小时后给小鼠注射Ep，可以证明股骨红系集落形成单位（CFU-E）、早幼红细胞数量以及59铁掺入股骨骨髓细胞的量均增加。这些发现，连同骨髓红系细胞对该激素的反应，提示内毒素注射后红细胞生成受抑制的机制是循环Ep水平降低。
