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