title: Differentiation-associated expression of two functionally distinct classes of granulocyte-macrophage colony-stimulating factor receptors by human myeloid cells.
abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF) activates a broad range of myeloid cells through binding to high affinity surface membrane receptors. The effects of this hematopoietin are dependent upon the differentiation status of the myeloid cell and range from proliferation of early myeloid progenitor cells to activation of neutrophil and monocyte function. In addition, many of the biological effects of GM-CSF are shared with interleukin-3 (IL-3), a distantly related lymphokine. In this study, we have characterized the GM-CSF receptor of myeloid cells at various stages of differentiation by comparing the binding characteristics and surface regulation of this receptor in early versus late myeloid cells. Scatchard analysis revealed a single class of high affinity receptors on normal neutrophils, monocytes, and myeloblasts from patients with acute myeloid leukemia. Neutrophils expressed significantly higher numbers of receptors, with an approximately 2-fold lower affinity, when compared with other myeloid cells. Two different patterns of GM-CSF receptor regulation and binding were observed. In the first pattern, the GM-CSF receptor of neutrophils was rapidly down-regulated by GM-CSF itself, by phorbol myristate acetate (PMA), and by the calcium ionophore A23187, and it was not competed for by IL-3 (class I receptor). In contrast to the neutrophil receptor, the GM-CSF receptor of the myeloblast demonstrated resistance to the down-regulatory effects of GM-CSF itself, PMA, and A23187, and it was completely competed for by IL-3 (class II receptor). In some cases of acute myeloid leukemia and monocytes, a mixed pattern of partial PMA responsiveness and partial competition by unlabeled IL-3 was observed, suggesting the coexpression of both class I and II receptors in these cells. In these cells, after down-regulation of the class I receptor by PMA, the remaining receptors were shown to be completely cross-competed for by IL-3, further supporting the hypothesis that these cells have a mixture of class I and II receptors. Chemical cross-linking of radiolabeled GM-CSF to myeloid cells revealed the labeling of three proteins (156, 126, and 82 kDa) which were identical in cells expressing either class I or II binding sites. These data show that there are differentiation-associated differences in the regulation of the GM-CSF receptor which may have important physiological consequences.
authors.affiliation: Division of Tumor Immunology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: S A
authors.initials: SA
authors.lastname: Cannistra
authors.forename: M
authors.initials: M
authors.lastname: Koenigsmann
authors.forename: J
authors.initials: J
authors.lastname: DiCarlo
authors.forename: P
authors.initials: P
authors.lastname: Groshek
authors.forename: J D
authors.initials: JD
authors.lastname: Griffin
mesh_terms: D001667:Binding, Competitive; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D003432:Cross-Linking Reagents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016184:Receptors, Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D003115:Colony-Stimulating Factors; D003432:Cross-Linking Reagents; D006133:Growth Substances; D007377:Interleukin-3; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate