Synergism of nitric oxide and maturation signals on human dendritic cells occurs through a cyclic GMP-dependent pathway

Nitric oxide (NO), generated by phagocytes at inflammation sites, contributes to regulate immune responses through autocrine and paracrine actions on bystander cells. Among the latter are dendritic cells (DCs). Little is known about regulation of DC function by NO, especially in the human system. We...

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Bibliographic Details
Published in:Journal of leukocyte biology 2003-02, Vol.73 (2), p.253-262
Main Authors: Paolucci, Clara, Burastero, Samuele E., Rovere‐Querini, Patrizia, De Palma, Clara, Falcone, Sestina, Perrotta, Cristiana, Capobianco, Annalisa, Manfredi, Angelo A., Clementi, Emilio
Format: Article
Language:English
Subjects:
CD40
CD40 Antigens - physiology
Cyclic GMP - physiology
Dendritic Cells - physiology
guanylate cyclase
Humans
IL‐12
Interleukin-12 - physiology
lipopolysaccharide
Lipopolysaccharides - pharmacology
Lymphocyte Activation
Nitric Oxide - physiology
T cell activation
T-Lymphocytes - immunology
TNF‐α
Tumor Necrosis Factor-alpha - pharmacology
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Summary:Nitric oxide (NO), generated by phagocytes at inflammation sites, contributes to regulate immune responses through autocrine and paracrine actions on bystander cells. Among the latter are dendritic cells (DCs). Little is known about regulation of DC function by NO, especially in the human system. We exposed human monocyte‐derived DCs to the NO donor (z)‐1‐[2‐(2‐aminoethyl)‐N‐(2‐ammonioethyl)amino] diazen‐1‐ium‐1,2 diolate (DETA‐NO) during their maturation process induced by treatment with tumor necrosis factor α or lipopolysaccharide or by CD40 activation. We report here that after exposure to DETA‐NO, DCs exhibit a significantly increased ability to activate T lymphocytes stimulated by mycobacterial antigens, Staphylococcus aureus Cowen strain B, allo‐antigens, or cross‐linking of the CD3–T cell receptor complex. This effect persists after removal of DETA‐NO, depends on the generation of cyclic guanosine 5′‐monophosphate, and is a result of enhanced release by DCs of soluble factors, in particular interleukin (IL)‐12. This modulation of DC function is a result of a synergism between NO and the various maturation stimuli, as neither enhanced T cell activation nor IL‐12 release was observed after DC exposure to DETA‐NO only. These results provide the first evidence that NO acts as a cosignaling molecule regulating human DC response to maturation stimuli.
ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.0902447