EVIDENCE FOR A ROLE OF FC-EPSILON-RII 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 cult ure with IL-4, human monocytes released detectable amounts of nitrite and L-citrulline that were inhibited in the presence of nitro-L-argini ne (1 mM). Incubation with an anti-CD23 mAb Fab fragment that suppress ed the biological effect of CD23 led to a strong reduction (50 to 70%) of the IL-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 suppre ssed by nitro-L-arginine. Preactivation of human monocytes with IFN-ga mma led to subsequent increased IL-4- and CD23-driven nitrite and L-ci trulline productions that were also suppressed in the presence of eith er nitro-L-arginine or the anti-CD23 mAb Fab fragment. The CD23 molecu le 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. (C) 1995 Academic Press, Inc.