CD38 expression and functional activities are up-regulated by IFN-gamma on human monocytes and monocytic cell lines

J Leukoc Biol. 2001 Apr;69(4):605-12.

Abstract

Human CD38, a surface molecule expressed by immature and activated T and B lymphocytes, has been characterized as a molecule transducing activation and proliferation signals, and intervening in adhesion to endothelium via its ligand CD31. CD38 is also a complex ectoenzyme featuring ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase activities, leading to the synthesis and degradation of cADPR, a Ca+-mobilizing agent. We investigated the effects of monocyte-activating stimuli (IFN-gamma, IL-2, LPS, TNF-alpha, and GM-CSF) on the expression and function of CD38, starting from the observation that human monocytes and the derived lines U937, THP-1, and Mono-Mac-6 bear the molecule on their surface. Our results indicate that IFN-gamma is a strong up-modulator of CD38, and IL-2 increases its expression only modestly. LPS, TNF-alpha, and GM-CSF had no detectable effects. Treatment with IFN-gamma produced a dose- and time-dependent up-regulation of CD38 in monocytes and monocytic lines, which was paralleled by increased ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase activities. Furthermore, CD38 ligation by specific MoAb reduced the IFN-gamma-dependent enhancement of monocyte-dynamic adhesion to endothelial monolayers. These findings identify IFN-gamma as a modulator of monocytic CD38 expression and indicate that CD38 plays a specific role in the activation and adhesion processes performed by monocytes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD*
  • Antigens, Differentiation / biosynthesis
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology
  • Antigens, Differentiation / physiology*
  • Calcium Signaling / drug effects
  • Cell Adhesion / drug effects
  • Cell Line
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / cytology
  • Enzyme Induction / drug effects
  • Gene Expression Regulation / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • HL-60 Cells / drug effects
  • HL-60 Cells / metabolism
  • Humans
  • Interferon-gamma / pharmacology*
  • Interleukin-10 / pharmacology
  • Interleukin-13 / pharmacology
  • Interleukin-2 / pharmacology
  • Interleukin-4 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Membrane Glycoproteins
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • NAD+ Nucleosidase / biosynthesis
  • NAD+ Nucleosidase / genetics
  • NAD+ Nucleosidase / immunology
  • NAD+ Nucleosidase / physiology*
  • Recombinant Proteins / pharmacology
  • Transforming Growth Factor beta / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology
  • U937 Cells / drug effects
  • U937 Cells / metabolism
  • Umbilical Veins

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • Interleukin-13
  • Interleukin-2
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • NAD+ Nucleosidase
  • ADP-ribosyl Cyclase 1