Park L S, Friend D, Gillis S, Urdal D L
J Exp Med. 1986 Jul 1;164(1):251-62. doi: 10.1084/jem.164.1.251.
125I-labeled recombinant human GM-CSF was used to identify and characterize receptors specific for this lymphokine on both a mature primary cell, human neutrophils, and on the undifferentiated promyelomonocytic leukemia cell line, HL-60. Human GM-CSF also bound to primary human monocytes and to the myelogenous leukemia cell line, KG-1, but not to any of the murine cells known to express the murine GM-CSF receptor. In addition, although some murine T lymphomas can express the GM-CSF receptor, none of the human cell lines of T cell lineage that we examined bound iodinated human GM-CSF. Binding to all cell types was specific and saturable. Equilibrium binding studies revealed that on all cell types examined, GM-CSF bound to a single class of high affinity receptor (100-500 receptors per cell) with a Ka of 10(9)-10(10)/M. More extensive characterization with neutrophils and HL-60 cells showed that in both cases, binding of GM-CSF was rapid at 37 degrees C with a slow subsequent dissociation rate that exhibited marked biphasic kinetics. Among a panel of lymphokines and growth hormones, only human GM-CSF could compete for binding of human 125I-GM-CSF to these cells. GM-CSF can not only stimulate the proliferation and differentiation of granulocyte/macrophage precursor cells, but can modulate the functional activity of mature granulocytes and macrophages as well. No significant differences in the kinetic parameters of receptor binding were seen between mature neutrophils and the undifferentiated promyelocytic leukemia cell line HL-60, indicating that maturation-specific responses to GM-CSF are not mediated by overt changes in the binding characteristics of the hormone for its receptor.
用¹²⁵I标记的重组人粒细胞-巨噬细胞集落刺激因子（GM-CSF）来鉴定和表征这种淋巴因子在成熟原代细胞——人中性粒细胞以及未分化的早幼粒细胞白血病细胞系HL-60上的特异性受体。人GM-CSF也能与人原代单核细胞以及骨髓性白血病细胞系KG-1结合，但不与任何已知表达鼠GM-CSF受体的鼠细胞结合。此外，尽管一些鼠T淋巴瘤能表达GM-CSF受体，但我们检测的所有T细胞系人细胞株均不结合碘化人GM-CSF。与所有细胞类型的结合都是特异性且可饱和的。平衡结合研究表明，在所检测的所有细胞类型上，GM-CSF都与一类单一的高亲和力受体结合（每个细胞有100 - 500个受体），解离常数Ka为10⁹ - 10¹⁰/M。对中性粒细胞和HL-60细胞进行更广泛的表征显示，在这两种情况下，GM-CSF在37℃时结合迅速，随后解离速率缓慢，呈现出明显的双相动力学。在一组淋巴因子和生长激素中，只有人GM-CSF能竞争人¹²⁵I-GM-CSF与这些细胞的结合。GM-CSF不仅能刺激粒细胞/巨噬细胞前体细胞的增殖和分化，还能调节成熟粒细胞和巨噬细胞的功能活性。成熟中性粒细胞和未分化的早幼粒细胞白血病细胞系HL-60之间在受体结合动力学参数上没有显著差异，这表明GM-CSF的成熟特异性反应不是由激素与其受体结合特性的明显变化介导的。
