REGULATION BY ENDOGENOUS INTERLEUKIN-10 OF THE EXPRESSION OF NITRIC OXIDE SYNTHASE INDUCED AFTER LIGATION OF CD23 IN HUMAN MACROPHAGES

The possible role of interleukin 10 (IL-10) as an endogenous inhibitor of CD23-driven inducible nitric oxide synthase (iNOS) expression in human macrophages was investigated. Cross-linking of CD23 by a monoclonal antibody induced iNOS mRNA, as detected by RT-PCR, and the production of NO measured as the stable derivative, nitrite. A linear correlation was observed between CD23 expression and iNOS activity or NO2- production. The iNOS activity reached a maximum 48 h after ligation of CD23, then declined rapidly until 72 h. In parallel, nitrite production was detected after 24 h and reached a maximum after 48 h. In addition, ligation of the CD23 molecule induced, in a time-dependent manner, the production of IL-10. As this cytokine is known to regulate iNOS induction and activity, we evaluated the effect of a neutralizing mAb to IL-10 on CD23-induced iNOS activity and nitrite production by CD23-bearing macrophages and found that both were significantly enhanced. Furthermore, the addition of exogenous IL-10 suppressed CD23-driven iNOS mRNA expression, iNOS activity and production of nitrite. These data suggest that, after CD23-ligation at the cell surface of human phagocytes, the secretion of IL-10 downregulates the CD23-induced NO production at the transcriptional level, thus providing an efficient feed-back mechanism.