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
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP-ribosyl Cyclase
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ADP-ribosyl Cyclase 1
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Antibodies, Monoclonal / pharmacology
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Antigens, CD*
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Antigens, Differentiation / biosynthesis
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Antigens, Differentiation / genetics
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Antigens, Differentiation / immunology
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Antigens, Differentiation / physiology*
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Calcium Signaling / drug effects
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Cell Adhesion / drug effects
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Cell Line
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Dose-Response Relationship, Drug
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Endothelium, Vascular / cytology
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Enzyme Induction / drug effects
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Gene Expression Regulation / drug effects
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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HL-60 Cells / drug effects
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HL-60 Cells / metabolism
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Humans
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Interferon-gamma / pharmacology*
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Interleukin-10 / pharmacology
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Interleukin-13 / pharmacology
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Interleukin-2 / pharmacology
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Interleukin-4 / pharmacology
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Lipopolysaccharides / pharmacology
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Membrane Glycoproteins
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Monocytes / drug effects*
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Monocytes / metabolism
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NAD+ Nucleosidase / biosynthesis
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NAD+ Nucleosidase / genetics
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NAD+ Nucleosidase / immunology
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NAD+ Nucleosidase / physiology*
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Recombinant Proteins / pharmacology
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Transforming Growth Factor beta / pharmacology
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Tumor Necrosis Factor-alpha / pharmacology
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U937 Cells / drug effects
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U937 Cells / metabolism
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Umbilical Veins
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation
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Interleukin-13
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Interleukin-2
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Lipopolysaccharides
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Membrane Glycoproteins
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Recombinant Proteins
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Transforming Growth Factor beta
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Tumor Necrosis Factor-alpha
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Interleukin-10
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Interleukin-4
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Interferon-gamma
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Granulocyte-Macrophage Colony-Stimulating Factor
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ADP-ribosyl Cyclase
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CD38 protein, human
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NAD+ Nucleosidase
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ADP-ribosyl Cyclase 1