Department of Functional Morphology, Nihon University School of Medicine, 30-1 Ohyaguchi-kami-machi, Itabashiku, Tokyo 173-8610, Japan.
Immunobiology. 2010 May;215(5):348-55. doi: 10.1016/j.imbio.2009.05.004. Epub 2009 Jul 9.
Neopterin is produced by monocytes and is a useful biomarker for inflammation. We found previously that neopterin enhanced myelopoiesis but suppressed B-lymphopoiesis triggered by the positive and negative regulations of cytokines produced by stromal cells in mice. The effects of neopterin on erythropoiesis during the enhancement of myelopoiesis were determined in the present study using C57BL/6J mice. The intravenous injection of neopterin into mice resulted in a prolonged decrease in the number of femoral erythroid progenitor cells (BFU-Es and CFU-Es), whereas the number of femoral myeloid progenitor cells (CFU-GMs) was increased. Interestingly, the oscillatory changes in the number of erythroid progenitor cells were reciprocal to those of myeloid progenitor cells. The expression of Cdc42, a regulator of the balance between erythropoiesis and myelopoiesis, was down-regulated, implying that the suppression of erythropoiesis is due to myelopoietic predominance. Furthermore, the expression of SDF-1 in stromal cells, a negative regulator of erythropoiesis, was up-regulated. These results suggest that neopterin facilitates myelopoiesis in the bone marrow by suppressing erythropoiesis, thereby contributing to the potential up-regulation of inflammatory process.
新蝶呤是由单核细胞产生的,是炎症的有用生物标志物。我们之前发现,新蝶呤增强髓系造血,但抑制由基质细胞产生的细胞因子的正、负调节触发的 B 淋巴细胞生成。本研究采用 C57BL/6J 小鼠,确定了新蝶呤在增强髓系造血过程中对红细胞生成的影响。静脉注射新蝶呤导致股骨红系祖细胞(BFU-Es 和 CFU-Es)数量持续减少,而股骨髓系祖细胞(CFU-GMs)数量增加。有趣的是,红细胞生成祖细胞数量的波动变化与髓系祖细胞的波动变化呈相反趋势。红细胞生成和髓系造血平衡的调节剂 Cdc42 的表达下调,表明红细胞生成的抑制是由于髓系优势所致。此外,基质细胞中 SDF-1 的表达上调,SDF-1 是红细胞生成的负调节剂。这些结果表明,新蝶呤通过抑制红细胞生成来促进骨髓中的髓系造血,从而有助于炎症过程的潜在上调。