NDLI: Regulation of surface expression of the granulocyte/macrophage colony-stimulating factor receptor in normal human myeloid cells.

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Regulation of surface expression of the granulocyte/macrophage colony-stimulating factor receptor in normal human myeloid cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Cannistra, S. A. Griffin, J. D. Garlick, R. Miller, J. Groshek, P.
Description	Author Affiliation: Cannistra SA ( Division of Tumor Immunology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.);
Abstract	Recombinant human granulocyte/macrophage colony-stimulating factor (GM-CSF) exerts stimulatory effects on hematopoietic cells through binding to specific, high-affinity receptors (Kd = 30-100 pM). By using radiolabeled GM-CSF with high specific activity, we have investigated the factors and mechanisms that regulate GM-CSF receptor expression in normal human neutrophils, monocytes, and partially purified bone marrow myeloid progenitor cells. The neutrophil GM-CSF receptor was found to rapidly internalize in the presence of ligand through a mechanism that required endocytosis. Out of a large panel of naturally occurring humoral factors tested, only GM-CSF itself, tumor necrosis factor, and formyl-Met-Leu-Phe were found to down-regulate neutrophil GM-CSF receptor expression after a 2-hr exposure at biologically active concentrations (95% +/- 1%, 34% +/- 5%, 48% +/- 8% receptor down-regulation, respectively). GM-CSF also down-regulated its own receptor on monocytes and myeloid progenitor cells. Since formyl-Met-Leu-Phe is known to stimulate neutrophil protein kinase C activity, we also tested the ability of protein kinase C agonists to modulate GM-CSF receptor expression. Phorbol 12-myristate 13-acetate, bryostatin-1, and 1,2-dioctanoylglycerol were found to induce rapid down-regulation of the GM-CSF receptor in neutrophils, monocytes, and partially purified myeloid progenitor cells, suggesting that this effect may be at least partially mediated by protein kinase C. These data suggest that certain activators of neutrophil function may negatively regulate their biological effects by inducing down-regulation of the GM-CSF receptor.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	1
Volume Number	87
Language	English
Publisher	National Academy of Sciences
Publisher Date	1990-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Colony-Stimulating Factors Metabolism Growth Substances Hematopoietic Stem Cells Monocytes Receptors, Cell Surface Biosynthesis Down-Regulation Endocytosis Granulocyte-Macrophage Colony-Stimulating Factor Pharmacology In Vitro Techniques Kinetics Neutrophils Genetics Receptors, Colony-Stimulating Factor Recombinant Proteins Reference Values Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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