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Related Experiment Videos

GM-CSF: receptor structure and transmembrane signaling.

J F DiPersio1, D W Golde, J D Gasson

  • 1Department of Medicine, UCLA Medical Center 90024.

International Journal of Cell Cloning
|January 1, 1990
PubMed
Summary

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances immune cell function and growth. This study identifies GM-CSF receptors on choriocarcinoma cells and details their modulation on neutrophils.

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Area of Science:

  • Immunology
  • Cell Biology
  • Hematology

Background:

  • Human granulocyte-macrophage colony-stimulating factor (GM-CSF) is a key cytokine regulating hematopoietic precursor cell growth and mature effector cell function.
  • GM-CSF exerts its biological actions through a single class of high-affinity receptors found on responsive cells.

Purpose of the Study:

  • To investigate the presence and characteristics of GM-CSF receptors on the JAR choriocarcinoma cell line.
  • To examine the regulation and functional priming effects of GM-CSF on neutrophils.

Main Methods:

  • Affinity cross-linking experiments were used to detect GM-CSF receptor species.
  • Wheat germ agglutinin-sepharose was employed to characterize the GM-CSF receptor as a glycoprotein.
  • Neutrophils were treated with phorbol esters and fMLP to study receptor downregulation.

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  • Functional assays assessed GM-CSF's priming effect on neutrophil responses to secondary stimuli.
  • Main Results:

    • The same 98 kDa cross-linked species of GM-CSF receptor was detected on JAR cells as on other responsive cells.
    • JAR cells exhibit a significantly increased number of low-affinity GM-CSF receptors (10,000 sites/cell, Kd ~1.5 nM).
    • GM-CSF receptors on neutrophils are dramatically downregulated by phorbol esters and fMLP, but not by phosphatidylinositol-dependent phospholipase C.
    • GM-CSF primes neutrophils for enhanced release of 3H-arachidonic acid, leukotriene B4, and platelet-activating factor.

    Conclusions:

    • The JAR choriocarcinoma cell line expresses GM-CSF receptors, suggesting potential roles in cancer biology.
    • GM-CSF receptor expression and function on neutrophils are subject to specific regulatory mechanisms.
    • GM-CSF plays a crucial role in priming neutrophils for augmented responses to inflammatory stimuli.