Physiologically significant effects of pH and oxygen tension on granulopoiesis
Physiologically significant effects of pH and oxygen tension on granulopoiesis
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DOI：
10.1016/s0301-472x(99)00150-2
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发表时间：
2000-03-01
影响因子：
2.6
通讯作者：
Miller, WM
中科院分区：
文献类型：
--
作者：
Hevehan, DL;Papoutsakis, ET;Miller, WM
目标。骨髓（BM）的粒细胞分化发生在pH和O-2张力（pO(2)）低于骨髓窦的区域。这表明在亚血管pH和PO2下，颗粒生成会增强。材料与方法。通过动员外周血CD34（+）细胞沿粒细胞途径，结合干细胞因子、白细胞介素3、白细胞介素6和g - csf，评估pH和pO(2)对粒细胞增殖、分化和粒细胞集落刺激因子受体（G-CSFR）表达的影响。在亚血管pH下，细胞扩增增强，在pH 7.07至7.21时产生的总细胞和CD15（亮）/CD11b（+）晚期中性粒细胞前体（髓细胞、化髓细胞、条带）的数量是pH 7.38时的两倍。随着增殖的增加，低pH加速了分化的速度。此外，总CD15（亮）/CD11b(-)（早幼髓细胞，早期髓细胞）和CD15（亮）/CD11b（+）细胞扩增在较低pO下增强(2)，每种细胞类型在5% O-2时产生的数量是20% O-2时的两倍。低pH和低pO(2)的影响是叠加的，因此在pH 7.21和5% O-2条件下，总细胞、CD15（亮）/CD11b（-）和CD15（亮）/CD11b（+）的产生比在pH 7.38和20% OL的标准造血培养条件下多3.5倍、2.4倍和4.0倍。低pH能更快地上调G-CSFR表面表达，而pO(2)对G-CSFR表达无影响。这些数据提供了令人信服的证据，证明pH和pO(2)在Bh I内的梯度在调节造血中起着重要作用，在低pH下，粒细胞细胞增殖和分化更快，部分原因可能是G-CSFR表达更快，通过控制pH和pO(2)来改变细胞发育的能力对优化中性粒细胞前体的体外生产具有重要意义。(C) 2000国际实验血液学学会。Elsevier Science Inc.出版。
Objective. Granulocyte differentiation in the bone marrow (BM) takes place in regions with lower pH and O-2 tension (pO(2)) than those in the BM sinuses. This suggests that granulopoiesis will be enhanced at subvascular pH and PO2.Materials and Methods. The effects of pH and pO(2) on granulocyte proliferation, differentiation, and granulocyte colony-stimulating factor receptor (G-CSFR) expression were evaluated using mobilized peripheral blood CD34(+) cells directed down the granulocytic pathway with stem cell factor, interleukin 3, interleukin 6, and G-CSF.Results. Cell expansion was enhanced at subvascular pH, with tw ice as many total cells and CD15(bright)/CD11b(+) late neutrophil precursors (myelocytes, metamyelocytes, bands) produced at pH 7.07 to 7.21 as was produced at pH 7.38. Low pH accelerated the rate of differentiation concomitant with this increase in proliferation. Also, total, CD15(bright)/CD11b(-) (promyelocytes, early myelocytes), and CD15(bright)/CD11b(+) cell expansion was enhanced at lower pO(2), with twice as many of each cell type produced at 5% O-2 as at 20% O-2. The effects of low pH and low pO(2) were additive, such that generation of total, CD15(bright)/CD11b(-), and CD15(bright)/CD11b(+) cells was 3.5-, 2.4-, and 4.0-fold greater at pH 7.21 and 5% O-2 than at the standard hematopoietic culture conditions of pH 7.38 and 20% OL. Low pH resulted in faster upregulation of G-CSFR surface expression, whereas pO(2) had no effect on G-CSFR expression.Conclusion. These data provide compelling evidence that pH and pO(2) gradients within the Bh I play significant roles in regulating hematopoiesis, More rapid granulocytic cell proliferation and differentiation at low pH may be explained in part by more rapid G-CSFR expression, The ability to alter cell development by manipulating pH and pO(2) has important implications for optimizing ex vivo production of neutrophil precursors. (C) 2000 International Society for Experimental Hematology. Published by Elsevier Science Inc.