CD38 expression and functional activities are up-regulated by IFN-gamma on human monocytes and monocytic cell lines.
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.
Musso
T
T
Department of Public Health and Microbiology, University of Turin, Italy. musso@molinette.unito.it
Deaglio
S
S
Franco
L
L
Calosso
L
L
Badolato
R
R
Garbarino
G
G
Dianzani
U
U
Malavasi
F
F
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology; D004790:Enzyme Induction / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009244:NAD+ Nucleosidase / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020298:U937 Cells / Q000187:drug effects / Q000378:metabolism; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018793:Interleukin-13; D007376:Interleukin-2; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1