Abstract
The effects of nitric oxide (NO) on human neutrophil chemotactic responses and release of interleukin (IL)-8 was studied. Neutrophils exposed to chemoattractants (IL-8, FMLP, leukotriene B4, and C5a) failed to show increases in intracellular guanosine 3',5'-cyclic monophosphate (cGMP), an indicator of NO production. Although NO increased cGMP in neutrophils, neither of two NO donors (sodium nitroprusside and 3-morpholino-sydonimine) nor a NO synthase inhibitor (N omega-nitro-L-arginine) altered FMLP- or IL-8-elicited neutrophil chemotaxis (P > .25 for all). However, lipopolysaccharide-induced IL-8 production was increased in a dose-dependent manner by a combination of sodium nitroprusside and N-acetylcysteine (P = .03) or by S-nitrosoglutathione (P = .004). NO-augmented IL-8 release was not reproduced by treating neutrophils with dibutyryl-cGMP. Up-regulation of IL-8 release by NO was associated with increased IL-8 mRNA levels (P = .009). These data suggest that NO does not directly affect neutrophil chemotaxis but may indirectly alter chemotactic responses by increasing IL-8 production via a cGMP-independent pathway.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylcysteine / pharmacology
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Cells, Cultured
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Chemotaxis*
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Complement C5a / pharmacology
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Cyclic GMP / metabolism
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Dibutyryl Cyclic GMP / pharmacology
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Dose-Response Relationship, Drug
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Ferricyanides / pharmacology
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Glutathione / analogs & derivatives
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Glutathione / pharmacology
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Humans
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Interleukin-8 / metabolism*
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Interleukin-8 / pharmacology
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Leukotriene B4 / pharmacology
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Lipopolysaccharides / pharmacology
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Molsidomine / analogs & derivatives
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Molsidomine / pharmacology
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N-Formylmethionine Leucyl-Phenylalanine / pharmacology
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Neutrophils / metabolism*
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Nitric Oxide / metabolism*
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Nitric Oxide Synthase / metabolism
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Nitroprusside / pharmacology
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Nitroso Compounds / pharmacology
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RNA, Messenger / metabolism
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S-Nitrosoglutathione
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Up-Regulation
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omega-N-Methylarginine / pharmacology
Substances
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Ferricyanides
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Interleukin-8
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Lipopolysaccharides
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Nitroso Compounds
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RNA, Messenger
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Nitroprusside
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Leukotriene B4
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omega-N-Methylarginine
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Nitric Oxide
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Dibutyryl Cyclic GMP
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S-Nitrosoglutathione
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N-Formylmethionine Leucyl-Phenylalanine
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linsidomine
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Complement C5a
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Molsidomine
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Nitric Oxide Synthase
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Glutathione
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Cyclic GMP
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potassium ferricyanide
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Acetylcysteine