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,vas 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 NO, 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 NOS 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. (C) 1998 Academic Press.