Role of nitric oxide in the promoting effect of HIV type 1 infection and of gp120 envelope glycoprotein on interleukin 4-induced IgE production by normal human mononuclear cells.
Increased levels of serum IgE have been described in HIV-1 infection; however, mechanisms implicated in this immunoglobulin production remain unknown. In this study, we demonstrate that in vitro infection of human peripheral blood mononuclear cells (PBMCs) by HIV-1 monocytotropic (Ba-L) or lymphocytotropic (LAI) strains promotes IL-4-induced IgE production, indicating that the HIV-1 infectious process may participate in the IgE production observed in vivo. The effect of membrane glycoproteins (gp160, gp120, and gp41) was also evaluated. It was found that gp120 specifically potentiates in a dose-dependent manner IL-4-induced IgE production and does not affect IL-4-induced IgG, IgA, or IgM production. In these experiments, gp160 was also found to upregulate IL-4-induced IgE production, whereas gp41 was ineffective. This effect of gp120, gp160, and HIV-1 infection on IgE synthesis was not observed in the absence of IL-4. In the presence of IL-4, the inducing effect of gp120 appeared to be indirect because gp120 did not modify purified B lymphocyte IgE production after IL-4 and anti-CD40 monoclonal antibody stimulation. As HIV-1 infection is associated with alterations of PBMC redox metabolism, the role of nitric oxide (NO) in this IgE production by human PBMCs was evaluated. In the presence of a specific inhibitor of NO synthase pathways (L-NAME), IgE production induced by IL-4 and gp120 was abolished. Taken together, these data indicate that HIV-1 envelope glycoprotein gp120 (and gp160) specifically enhances IL-4-induced IgE production by normal human PBMCs, probably through the regulation of the nitric oxide pathway.
Dugas
N
N
Laboratorie Virus, Neurone, et Immunité, Faculté de Médecine Paris Sud, Le Kremlin Bicêtre, France. nathalie.dugas@kb.u-psud.fr
Dereuddre-Bosquet
N
N
Goujard
C
C
Dormont
D
D
Tardieu
M
M
Delfraissy
J F
JF
D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000494:pharmacology; D019302:HIV Envelope Protein gp160 / Q000276:immunology / Q000494:pharmacology; D015700:HIV Envelope Protein gp41 / Q000276:immunology / Q000494:pharmacology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000276:immunology* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D009569:Nitric Oxide / Q000502:physiology*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology
D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D011994:Recombinant Proteins; D015847:Interleukin-4; D009569:Nitric Oxide; D007073:Immunoglobulin E