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真性红细胞增多症。IV. 干细胞因子与正常及真性红细胞增多症高度纯化的红系祖细胞的特异性结合。

Polycythaemia vera. IV. Specific binding of stem cell factor to normal and polycythaemia vera highly purified erythroid progenitor cells.

作者信息

Dai C H, Krantz S B, Koury S T, Kollar K

机构信息

Department of Medicine, Hematology Division, Department of Veterans Affairs Medical Center, Nashville, Tennessee.

出版信息

Br J Haematol. 1994 Nov;88(3):497-505. doi: 10.1111/j.1365-2141.1994.tb05065.x.

Abstract

Polycythaemia vera (PV) patients' blood burst-forming units-erythroid (BFU-E) have an enhanced sensitivity to stem cell factor (SCF) compared to normal BFU-E. To characterize SCF receptors on erythroid progenitors from normal individuals and PV patients, we performed binding experiments using radioiodinated recombinant SCF (rSCF), day 1 BFU-E and day 8 erythroid colony-forming cells (ECFC), which are mostly colony-forming units-erythroid (CFU-E). 125I-rSCF binds to a single class of cell surface receptors (23,000/ECFC) at 0 degrees C with a high-binding affinity (Kd = 17 pM). Saturation occurred at 0.5 nM (10 ng/ml) which produces a nearly maximum biological effect. One half of the radiolabelled rSCF was internalized by the cells after 30 min at 37 degrees C. No significant differences in the receptor number, dissociation constant, or internalization rate were found between normal and PV ECFC. Autoradiographic analysis of 125I-rSCF binding to normal BFU-E and ECFC showed that no differences were present in either the percentage of positive cells or the number of radioactive grains/cell between the normal and PV erythroid progenitors. The enhanced sensitivity of PV BFU-E and CFU-E to SCF does not appear to be related to changes in SCF receptor number, binding affinity or internalization and the hypersensitivity of PV erythroid progenitors to SCF must reside in a further internal cellular abnormality.

摘要

真性红细胞增多症(PV)患者的血液红系爆式集落形成单位(BFU-E)与正常BFU-E相比,对干细胞因子(SCF)的敏感性增强。为了表征正常个体和PV患者红系祖细胞上的SCF受体,我们使用放射性碘化重组SCF(rSCF)、第1天的BFU-E和第8天的红系集落形成细胞(ECFC,其大多为红系集落形成单位(CFU-E))进行了结合实验。125I-rSCF在0℃时以高结合亲和力(Kd = 17 pM)与一类细胞表面受体(23,000/ECFC)结合。在0.5 nM(10 ng/ml)时出现饱和,这产生了几乎最大的生物学效应。在37℃下30分钟后,一半的放射性标记rSCF被细胞内化。正常和PV ECFC之间在受体数量、解离常数或内化速率方面未发现显著差异。对125I-rSCF与正常BFU-E和ECFC结合的放射自显影分析表明,正常和PV红系祖细胞在阳性细胞百分比或每个细胞的放射性颗粒数量方面均无差异。PV BFU-E和CFU-E对SCF的敏感性增强似乎与SCF受体数量、结合亲和力或内化的变化无关,PV红系祖细胞对SCF的超敏性必定存在于细胞内部的进一步异常中。

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