Involvement of Fcε:RII/CD23 and L-argininedependent pathway in IgE-mediated stimulation of human monocyte functions

Abstract

Elevated IgE levels are commonly observed during the inflammatory responses in allergy and a variety of infections. This Ig activates the release of multiple mediators from monocytes/macrophages. In the present work, we attempted to clarify the IgE-dependent events involved in the activation of monocyte functions. IgE-anti-IgE immune complexes induce the production of tumor necrosis factor-alpha, oxygen radicals, IL-6 and thromboxane B2 from normal human purified monocytes. Expression and cross-linkage of Fc epsilon RII/CD23 were essential for these IgE-mediated effects. Cytokine production following CD23 ligation depended on nitric oxide transduction pathway, as it was inhibited by NG-monomethyl-L-arginine, a competitive inhibitor of the conversion of L-arginine to L-citroline by nitric oxide synthase. Furthermore, addition of the nitric oxide chemical donator, Sin-1, enhanced IgE-induced monokine release. CD23-ligation also induced the production of nitrites by these cells. This work linked CD23 to the L-arginine-dependent transduction pathway and shows their involvement in IgE-mediated stimulation of human monocytes.

The killing of Leishmania major by human macrophages is mediated by nitric oxide induced after ligation of the Fc epsilon RII/CD23 surface antigen.

“…The optimal concentrations of these reagents regulating macrophage functions were determined in a preliminary analysis. SOD and catalase concentrations used in the present work were able to reduce the amount of superoxide produced by LPS in human macrophages by >80%, as determined by a chemiluminescence method (data not shown), described in detail elsewhere (18). Some infected cultures were treated with the NOS inhibitor L-NMMA or its inactive isomer D-NMMA for 1 h before IgE, as well as during anti-IgE treatment.…”

“…We have recently established that in human monocytes (18), eosinophils (19), acute myeloid leukemia cells (20), and CD23+ epidermal keratinocytes (21) ligation of the b isoform of CD23 by IgE and anti-IgE (IgE-anti-IgE immune complexes, or IgE-IC) or by a specific monoclonal antibody (mAb) to CD23 (CD23 mAb) promotes the generation of cGMP. Simultaneous measurement of the generation of nitrite (NO-j) indicated that the enhanced production of cGMP is consequent to activation of the L-arginine:NO pathway.…”

Bacterial infection induces nitric oxide synthase in human neutrophils.

“…Recently, neutrophils within human buffy coat preparations stimulated with a mixture of interleukin-1, tumor necrosis factor ␣, and interferon-␥ were shown to contain iNOS mRNA and protein, however iNOS was detected in only 20% of the stimulated neutrophils (41). Studies with monocytes/macrophages indicate that these cells can produce NO after infection with mycobacteria (17) or human immunodeficiency virus type I (42) and also after cross-linking of the surface receptor CD69 (43) or ligation of Fc⑀II/CD23 (44,45). Because NO is increased under conditions where the inducing agents are undefined, the combination of microbial products and cytokines, that induces iNOS in human disease states, warrants further investigation.…”

Expression of the inducible NO synthase in human monocytic U937 cells allows high output nitric oxide production

“…However, in most of these and other studies, the production of NO by stimulated human macrophages, measured by the Griess reaction, was nonexistent [43][44][45][46] (and our experience) or remarkably modest [23,[47][48][49] when compared to that of activated murine macrophages [5,33,50]. Weinberg et al [30] reported that human peripheral blood monocytes failed to produce NO x Ϫ when cultured with classical inducers of iNOS including cytokines (IL-1, 2, 4, 6, 7, IFN-␥, TNF-␣), growth factors (granulocyte-macrophage colony-stimulating factor), endotoxin, vitamin D 3 , or pathogens (Mycobacterium tuberculosis, Listeria monocytogenes, Candida albicans, M. avium); however, others, using nonclassical stimuli such as tumors [51], IgE-antiIgE complexes or anti-CD23 antibody [52,53], anti-CD69 antibody [54], gp120 from HIV [55], or polyribonucleotides [56], reported low but significant levels of NO production. Thus it can be concluded from these observations that conditions allowing high NO output by human macrophages are still unresolved.…”