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

Journal Article · Mon Jan 01 04:00:00 EST 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.1.93· OSTI ID:6941271

Cannistra, S A; Groshek, P; Griffin, J D ^[1]; Garlick, R; Miller, J ^[2]

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1. Harvard Medical School, Boston, MA (USA)
2. DuPont/New England Nuclear, Boston, MA (USA)

Recombinant human granulocyte/macrophage colony-stimulating factor (GM-CSF) exerts stimulatory effects on hematopoietic cells through binding to specific, high-affinity receptors. By using radiolabeled GM-CSF with high specific activity, the authors 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. Since formyl-Met-Leu-Phe is known to stimulate neutrophil protein kinase C activity, they 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.

• OSTI ID: 6941271
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:1; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BONE MARROW CELLS
CONNECTIVE TISSUE CELLS
ELEMENTS
ENZYMES
HALOGENS
HEMATOPOIETIC SYSTEM
IODINE
ISOTOPE APPLICATIONS
KINETICS
LEUKOCYTES
MACROPHAGES
MAMMALS
MAN
MATERIALS
MEMBRANE PROTEINS
NONMETALS
ORGANIC COMPOUNDS
PHAGOCYTES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PRIMATES
PROTEINS
RADIORECEPTOR ASSAY
REACTION KINETICS
RECEPTORS
SOMATIC CELLS
TRACER TECHNIQUES
TRANSFERASES
VERTEBRATES