CD38 ligation plays a direct role in the induction of IL-1beta, IL-6, and IL-10 secretion in resting human monocytes.
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.
Lande
Roberto
R
Department of Bacteriology and Medical Mycology, Istituto Superiore di Sanitá, 00161, Rome, Italy
Urbani
Francesca
F
Di Carlo
Beatrice
B
Sconocchia
Giuseppe
G
Deaglio
Silvia
S
Funaro
Ada
A
Malavasi
Fabio
F
Ausiello
Clara M
CM
D036541:ADP-ribosyl Cyclase / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D051997:ADP-ribosyl Cyclase 1; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D001704:Biopolymers; D002460:Cell Line; D019281:Dimerization; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008562:Membrane Glycoproteins; D009000:Monocytes / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000276:immunology; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001704:Biopolymers; D007140:Immunoglobulin Fab Fragments; D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017452:Receptors, IgG; D016753:Interleukin-10; D007371:Interferon-gamma; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1