Evidence for a Role of FcϵRII/CD23 in the IL-4-Induced Nitric Oxide Production by Normal Human Mononuclear Phagocytes

IL-4 stimulates NO production by human monocytes. After 6 days of culture with IL-4, human monocytes released detectable amounts of nitrite and L-citrulline that were inhibited in the presence of nitro-L-arginine (1 mM). Incubation with an anti-CD23 mAb Fab fragment that suppressed the biological effect of CD23 led to a strong reduction (50 to 70%) of the lL-4-Induced nitrite and L-citrulline production. Ligation of membrane-associated CD23 or stimulation with recombinant soluble CD23 elicited monocytes to release nitrite and L-citrulline that was suppressed by nitro-L-arginine. Preactivation of human monocytes with IFN-γ led to subsequent increased IL-4- and CD23-driven nitrite and L-citrulline productions that were also suppressed in the presence of either nitro-L-arginine or the anti-CD23 mAb Fab fragment. The CD23 molecule under its membrane or soluble form thus regulates NO generation by human monocytes. In addition, the IL-4-induced NO production could be mediated, at least in part, by CD23.