Premium
Synergism of nitric oxide and maturation signals on human dendritic cells occurs through a cyclic GMP‐dependent pathway
Author(s) -
Paolucci Clara,
Burastero Samuele E.,
RovereQuerini Patrizia,
De Palma Clara,
Falcone Sestina,
Perrotta Cristiana,
Capobianco Annalisa,
Manfredi Angelo A.,
Clementi Emilio
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0902447
Subject(s) - autocrine signalling , nitric oxide , microbiology and biotechnology , biology , paracrine signalling , lipopolysaccharide , immune system , guanosine , inflammation , cd40 , dendritic cell , monocyte , t cell , receptor , immunology , cytotoxic t cell , biochemistry , in vitro , endocrinology
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.