EXPRESSION AND DYNAMIC MODULATION OF THE HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR-RECEPTOR IN IMMATURE AND DIFFERENTIATED MYELOID CELLS
EXPRESSION AND DYNAMIC MODULATION OF THE HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR-RECEPTOR IN IMMATURE AND DIFFERENTIATED MYELOID CELLS
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DOI：
10.1111/j.1365-2141.1993.tb03164.x
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发表时间：
1993-10-01
影响因子：
6.5
通讯作者：
LINCH, DC
中科院分区：
文献类型：
--
作者：
KHWAJA, A;CARVER, J;LINCH, DC
在这项研究中，我们已经检查了表达和调制的人粒细胞集落刺激因子（G-CSF）受体（R）在未成熟和分化的骨髓细胞使用I-125标记的人G-CSF类似物（TG 50）。平衡结合数据显示，在表达G-CSFR的所有细胞类型上，受体的单一亲和力类别（K（D）235-606 pm），中性粒细胞表达2883 +/- 672 Rs/细胞。在未成熟细胞（U937）和中性粒细胞中检测到37 ℃时表面受体结合配体的快速内化，5分钟内特异性结合配体内化> 70%。浓度-反应数据显示，37 ℃时中性粒细胞G-CSFRs被配体占据的水平约为平衡结合数据预测的5倍，并与浓度密切相关。生物活性的响应数据。未检测到通过内化下调后G-CSFRs的再表达。在37 ℃下观察到嗜中性粒细胞G-CSFR被几种试剂下调，包括粒细胞-巨噬细胞集落刺激因子（GM-CSF）、肿瘤坏死因子（TNF）、脂多糖（LPS）、f-met-leu-phe（fMLP）、佛波醇酯（TPA）和C5 a，但在4 ℃下未观察到。相反，未成熟髓系细胞上的G-CSFRs仅被TPA显著下调。用DMSO（一种常用的粒细胞分化模型）分化髓性白血病细胞系HL-60与G-CSFR表达显著降低（对照组的11 +/- 5%）相关，而用维甲酸处理导致G-CSFR表达增加（161 +/- 3%）。
In this study we have examined the expression and modulation of the human granulocyte colony-stimulating factor (G-CSF) receptor (R) in immature and differentiated myeloid cells using a I-125 labelled human G-CSF analogue (TG50). Equilibrium binding data revealed a single affinity class of receptor on all cell types expressing G-CSFR (K(D) 235-606 pm) with neutrophils expressing 2883 +/- 672 Rs/cell. Rapid internalization of surface receptor-bound ligand at 37-degrees-C was detected in both immature cells (U937) and neutrophils with > 70% of specifically bound ligand internalized within 5 min. Concentration-response data showed that the level of occupancy of neutrophil G-CSFRs by ligand at 37-degrees-C was approximately 5-fold greater than predicted by equilibrium binding data and correlated closely with concentration-response data for biological activity. Re-expression of G-CSFRs following down-regulation by internalization was not detected. Down-regulation of the neutrophil G-CSFR by several agents including granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF), lipopolysaccharide (LPS), f-met-leu-phe (fMLP), phorbol ester (TPA) and C5a was observed at 37-degrees-C but not at 4-degrees-C. In contrast, G-CSFRs on immature myeloid cells were significantly down-regulated by TPA only. Differentiation of myeloid leukaemic cell line HL-60 with DMSO, a frequently used model of granulocytic differentiation, was associated with a significant reduction in G-CSFR expression (11 +/- 5% of control) whereas treatment with retinoic acid led to increased G-CSFR expression (161 +/- 3%).