Characterization of receptors for human colony-stimulating factor (GM-CSF and IL-3)

GM-CSF和EL-3可作用于多种造血细胞并支持其生长和分化。尽管它们的生物学作用是显著的，但对其细胞内信号通路的分子机制知之甚少。在本研究中，我们已经证明GM-CSF的高亲和力结合位点被IL-3的加入部分阻断。我们还发现GM-CSF的低亲和力受体不仅在造血细胞中表达，而且在人绒毛膜癌细胞系中也表达。此外，GM-CSF可诱导该细胞株产生促性腺激素。因此，1E可能是GM-CSF的低亲和力受体本身可以转导一些信号。近年来，许多淋巴因子的可溶性受体已被发现。这些可溶性受体被认为具有重要的生物学作用，如膜受体的竞争性抑制剂。我们。表明存在一种可溶性的GMCSF受体。在人绒毛膜癌细胞系的上清液中发现一种62 kDa的可溶性蛋白可与^<125> i标记的GM-CSF结合。这种结合被过量添加的非标记GM-CSF特异性阻断。我们在造血细胞的上清中不能识别这种类型的受体。这种可溶性GM-CSF受体的结构和生物学作用目前正在研究中。

GM-CSF and EL-3 can act on a broad range of hematopoietic cells and support their growth and differentiation. Although their biological role is striking, little is known about the molecular mechanism of their intracellular signaling pathway. In this study, we have demonstrated that high affinity-binding site of GM-CSF is partially blocked by the addition of IL-3.We have also shown that low affinity receptor for GM-CSF is expressed not only in hematopoietic cells but also in a human choriocarcinoma line. Furthen-nore, addition of GM-CSF to this cell line could induce the production of gonadotropin. Therefore, 1E is likely that low affinity receptor for GM-CSF itself can transduce some signals.Recently, soluble type of receptors has been identified for many lymphokines. These soluble receptors are presumed to have significant biological role, such as competitive inhibitor of membrane receptor. We. could reveal that there is a soluble type of GMCSF receptor. A soluble protein of 62 kDa in the supernatant of a human choriocarcinoma cell line was shown to bind to ^<125>I-labeled GM-CSF. This binding was specifically blocked by the excess addition of non-labeled GM-CSF. We could not recognize this type of receptor in the supernatant of hematopoietic cells.The structure and the biological role of this soluble GM-CSF receptor is currently under investigation.