CD38 ligation plays a direct role in the induction of IL-1beta, IL-6, and IL-10 secretion in resting human monocytes

Cell Immunol. 2002 Nov;220(1):30-8. doi: 10.1016/s0008-8749(03)00025-x.

Abstract

CD38 signaling, either induced by ligation with specific agonistic monoclonal antibody (mAb) or after interaction with CD31, its cognate counter-receptor, is involved in release of IL-1beta, IL-6, and IL-10 cytokines in resting human monocytes. CD38 ligation by the F(ab')(2) IB4 mAb did not induce signals relevant for cytokine secretion and the block of the Fcgamma receptor I (FcgammaRI) by anti-CD64 or FcgammaRII by anti-CD32 mAb did not inhibit CD38-mediated IL-1beta release. Dimerization or multimerization of the CD38 molecule by: (i) cross-linking of the receptor ligated by F(ab')(2) or by (ii) increasing CD38 expression by treating monocytes with IFNgamma were able to restore the truncated CD38-mediated signals involved in cytokine secretion. These data indicate that CD38 receptor-mediated signals operate directly suggesting a Fcgamma receptorial surface molecule independent activation pathway. The key element for the receptor mediated signaling is represented by surface density of CD38 on resting monocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase / chemistry
  • ADP-ribosyl Cyclase / immunology
  • ADP-ribosyl Cyclase / physiology*
  • ADP-ribosyl Cyclase 1
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD / chemistry
  • Antigens, CD / immunology
  • Antigens, CD / physiology*
  • Biopolymers
  • Cell Line
  • Dimerization
  • Humans
  • Immunoglobulin Fab Fragments / immunology
  • Interferon-gamma / pharmacology
  • Interleukin-1 / metabolism*
  • Interleukin-10 / metabolism*
  • Interleukin-6 / metabolism*
  • Membrane Glycoproteins
  • Monocytes / metabolism*
  • Platelet Endothelial Cell Adhesion Molecule-1 / physiology
  • Receptors, IgG / antagonists & inhibitors
  • Receptors, IgG / immunology
  • Signal Transduction

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Biopolymers
  • Immunoglobulin Fab Fragments
  • Interleukin-1
  • Interleukin-6
  • Membrane Glycoproteins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Receptors, IgG
  • Interleukin-10
  • Interferon-gamma
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1