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Related Experiment Videos

Signaling through CD38 induces NK cell activation.

R Mallone1, A Funaro, M Zubiaur

  • 1Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, University of Torino, 10126 Torino, Italy.

International Immunology
|April 3, 2001
PubMed
Summary

CD38 ligation on human NK cells triggers calcium mobilization, HLA class II and CD25 expression, and phosphorylation. This signaling induces cytokine release and cytolytic functions, similar to CD16 activation.

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Area of Science:

  • Immunology
  • Cell Biology
  • Signal Transduction

Background:

  • Human CD38 is a signal transduction molecule and ectoenzyme.
  • CD38's role in Natural Killer (NK) cells remains largely uncharacterized.
  • CD38 modulates intracellular calcium levels via cyclic ADP-ribose (cADPR).

Purpose of the Study:

  • To investigate the functional role of CD38 in human NK cells.
  • To elucidate the signaling pathways activated by CD38 ligation in NK cells.
  • To compare CD38-mediated signaling with CD16 (FcgammaRIIIA) signaling in NK cells.

Main Methods:

  • Analysis of intracellular calcium levels upon CD38 ligation.
  • Assessment of HLA class II and CD25 expression using flow cytometry.
  • Investigation of tyrosine phosphorylation of signaling molecules (ZAP-70, c-Cbl) via Western blotting.

Related Experiment Videos

  • Measurement of cytokine (IFN-gamma, GM-CSF) production at mRNA and protein levels.
  • Evaluation of NK cell cytotoxicity and ultrastructural changes post-activation.
  • Comparison of CD38 and CD16 signaling pathways in NK cells and NK-derived cell lines.

    • Main Results:

    • CD38 ligation induced a significant increase in intracellular Ca2+ levels.
    • Upregulation of HLA class II and CD25 expression was observed.
    • Tyrosine phosphorylation of CD3-zeta, FcepsilonRIgamma, ZAP-70, and c-Cbl occurred.
    • CD38 signaling promoted the release of IFN-gamma and GM-CSF.
    • CD38 activation enhanced NK cell cytolytic activity after IL-2 treatment.
    • CD38-mediated Ca2+ mobilization was dependent on CD16 expression.

    Conclusions:

    • CD38 ligation initiates significant signaling events in human NK cells.
    • CD38 signaling pathways in NK cells share similarities with those of CD16.
    • CD38 plays a crucial role in modulating NK cell activation and effector functions.