IMMUNOGLOBULIN-E DINITROPHENYL COMPLEXES INDUCE NITRIC-OXIDE SYNTHESIS IN RAT PERITONEAL-MACROPHAGES BY A MECHANISM INVOLVING CD23 AND NF-KAPPA-B ACTIVATION/

The production of nitric oxide (NO) by rat adherent peritoneal cells s timulated with preformed IgE/Dinitrophenyl-BSA (DNP-BSA) complexes and its dependence on the activation of the transcription factor NF-kappa B were studied, Stimulation with IgE/DNP-BSA complexes at equivalence induced both the production of NO and an increased expression of the inducible isoform of NO synthase (iNOS) protein. Both events were also elicited by a rabbit polyclonal F(ab')(2) anti-CD23 cross-reacting wi th rat CD23, thus suggesting Fc epsilon RII/CD23 antigen as the IgE-bi nding structure involved in the triggering of the response and ruling out an interaction of the antibody via its Fc portion, Inhibition of r edox-sensitive signaling mechanisms by the antioxidant pyrrolidine dit hiocarbamate (PDTC) blocked NO production, iNOS expression, and NF-kap pa B activation elicited by both IgE/DNP-BSA complexes and anti-CD23 F (ab')(2), thus suggesting the involvement of NF-kappa B in the signali ng pathway leading to the transcriptional activation of iNOS, These re sults show the existence in rat peritoneal macrophages of a signaling pathway triggered by CD23 engagement that promotes nuclear translocati on of NF-kappa B and transcriptional activation of the inducible isofo rm of NO synthase, (C) 1998 Academic Press.