Regulatory role of nitric oxide in the IL-4-induced IgE production by normal human peripheral blood mononuclear cells.
An in vitro study was performed in order to assess a possible regulatory role of nitric oxide (NO), a short-lived biologic mediator that displays immunoregulatory properties, in the IL-4-driven synthesis of IgE by normal human peripheral blood mononuclear cells (PBMC). In addition to induce IgE production, IL-4 was found to elicit nitrite (NO2-) release by PBMC. A marked correlation was observed between IgE secretion and nitrite release by PBMC stimulated with an optimal concentration of IL-4. The IL-4-dependent IgE production was significantly reduced (p < 0.001) in the presence of N omega-monomethyl-L-arginine (LNMMA), an inhibitor of the NO-synthase pathway; this inhibition was partially reverted with an excess of L-arginine. Addition to PBMC cultures of the chemical NO donor Sin-1, inactive alone, was found to result, depending on the concentration of IL-4, in either potentiation (suboptimal concentration of IL-4, 10 ng/ml) or inhibition (optimal concentration of IL-4, 50 ng/ml) of IgE synthesis. The potentiating effect of Sin-1 was dose dependent, with a maximal effect for 300 microM, whereas its metabolite Sin-1c was inactive. In both cases, Sin-1 markedly reduced the IL-4-induced release of the soluble form of the low affinity IgE receptor (sCD23). Together, these data strongly suggest that NO may display biphasic immunoregulatory properties on the IL-4-induced IgE production by PBMC.
INSERUM U313, Hôpital Pitié-Salpêtrière, Paris, France.
N
N
Paul-Eugène
J P
JP
Kolb
C
C
Damais
K
K
Yamaoka
B
B
Dugas
D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D017455:Receptors, IgE / Q000378:metabolism; D019323:omega-N-Methylarginine
D009573:Nitrites; D016877:Oxidants; D017455:Receptors, IgE; D015847:Interleukin-4; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007073:Immunoglobulin E; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine