Role of IgE immune complexes in the regulation of HIV-1 replication and increased cell death of infected U1 monocytes: involvement of CD23/Fc epsilon RII-mediated nitric oxide and cyclic AMP pathways.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Role of IgE immune complexes in the regulation of HIV-1 replication and increased cell death of infected U1 monocytes: involvement of CD23/Fc epsilon RII-mediated nitric oxide and cyclic AMP pathways.

Mol Med. 1996 Jan;2(1):38-49. Unique Identifier : AIDSLINE MED/97056193
Ouaaz F; Ruscetti FW; Dugas B; Mikovits J; Agut H; Debre P; Mossalayi MD; Molecular Immuno-hematology Group, CNRS URA625,; Pitie-Salpetriere Hospital, Paris, France.

Abstract: BACKGROUND: IgE/anti-IgE immune complexes (IgE-IC) induce the release of multiple mediators from monocytes/macrophages and the monocytic cell line U937 following the ligation of the low-affinity Fc epsilon receptors (Fc epsilon RII/CD23). These effects are mediated through an accumulation of cAMP and the generation of L-arginine-dependent nitric oxide (NO). Since high IgE levels predict more rapid progression to acquired immunodeficiency syndrome, we attempted to define the effects of IgE-IC on human immunodeficiency virus (HIV) production in monocytes. MATERIALS AND METHODS: Two variants of HIV-1 chronically infected monocytic U1 cells were stimulated with IgE-IC and virus replication was quantified. NO and cAMP involvement was tested through the use of agonistic and antagonistic chemicals of these two pathways. RESULTS: IgE-IC induced p24 production by U1 cells with low-level constitutive expression of HIV-1 mRNAs and extracellular HIV capsid protein p24 levels (U1low), upon their pretreatment with interleukin 4 (IL-4) or IL-13. This effect was due to the crosslinking of CD23, as it was reversed by blocking the IgE binding site on CD23. The IgE-IC effect could also be mimicked by crosslinking of CD23 by a specific monoclonal antibody. p24 induction by IgE-IC was then shown to be due to CD23-mediated stimulation of cAMP, NO, and tumor necrosis factor alpha (TNF alpha) generation. In another variant of U1 cells with > 1 log higher constitutive production of p24 levels (U1high), IgE-IC addition dramatically decreased all cell functions tested and accelerated cell death. This phenomenon was reversed by blocking the nitric oxide generation. CONCLUSIONS: These data point out a regulatory role of IgE-IC on HIV-1 production in monocytic cells, through CD23-mediated stimulation of cAMP and NO pathways. IgE-IC can also stimulate increased cell death in high HIV producing cells through the NO pathway.

Keywords: Antigen-Antibody Complex/*IMMUNOLOGY/PHARMACOLOGY Cell Death/*GENETICS Cyclic AMP/PHARMACOLOGY Electrophoresis, Polyacrylamide Gel Fluorescent Antibody Technique Gene Expression Regulation/GENETICS Human HIV-1/*GENETICS/METABOLISM IgE/*IMMUNOLOGY/METABOLISM Monocytes/*METABOLISM Nitric Oxide/METABOLISM/PHARMACOLOGY Receptors, IgE/METABOLISM RNA, Messenger/ANALYSIS/METABOLISM Signal Transduction Virus Replication/GENETICS JOURNAL ARTICLE
970228
M9721920

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