LIGATION OF CD23 ACTIVATES SOLUBLE GUANYLATE-CYCLASE IN HUMAN MONOCYTES VIA AN L-ARGININE-DEPENDENT MECHANISM

Transduction through Fc epsilon R(2)/CD23 was analyzed in normal human monocytes using immunoglobulin E (IgE)-anti-IgE immune complexes (IgE ICs) and monoclonal antibodies (mAbs) to CD23. Anti-CD23 mAb and IgE IC triggered a time-dependent increase in cGMP and cAMP in interleukin -4-preincubated (CD 23(+)) but not in unstimulated (CD23(-)) monocytes . Maximal cGMP and cAMP accumulations were observed 10 and 20 min, res pectively, after the onset of CD23 ligation. The increase in cGMP was inhibited with N omega-monomethyl-L-arginine (L-NMMA), which also part ially affected cAMP accumulation. Addition of an anti-CDP3 mAb Fab fra gment inhibited the IgE IC- and the anti-CD23 mAb-induced cGMP and cAM P accumulation, confirming the engagement of CD23. In addition, IgE IC and anti-CDP3 mAb induced, at least in some donors, a production of n itrite that was inhibited in the presence of L-NMMA. Taken together, t hese findings suggest a possible involvement of the nitric oxide synth ase pathway in IgE IC-mediated activation of CD23(+) monocytes.