Effects of nitric oxide on chemotaxis and endotoxin-induced interleukin-8 production in human neutrophils

J Infect Dis. 1998 Jan;177(1):116-26. doi: 10.1086/513829.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcysteine / pharmacology
  • Cells, Cultured
  • Chemotaxis*
  • Complement C5a / pharmacology
  • Cyclic GMP / metabolism
  • Dibutyryl Cyclic GMP / pharmacology
  • Dose-Response Relationship, Drug
  • Ferricyanides / pharmacology
  • Glutathione / analogs & derivatives
  • Glutathione / pharmacology
  • Humans
  • Interleukin-8 / metabolism*
  • Interleukin-8 / pharmacology
  • Leukotriene B4 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Molsidomine / analogs & derivatives
  • Molsidomine / pharmacology
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / metabolism*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Nitroprusside / pharmacology
  • Nitroso Compounds / pharmacology
  • RNA, Messenger / metabolism
  • S-Nitrosoglutathione
  • Up-Regulation
  • omega-N-Methylarginine / pharmacology

Substances

  • Ferricyanides
  • Interleukin-8
  • Lipopolysaccharides
  • Nitroso Compounds
  • RNA, Messenger
  • Nitroprusside
  • Leukotriene B4
  • omega-N-Methylarginine
  • Nitric Oxide
  • Dibutyryl Cyclic GMP
  • S-Nitrosoglutathione
  • N-Formylmethionine Leucyl-Phenylalanine
  • linsidomine
  • Complement C5a
  • Molsidomine
  • Nitric Oxide Synthase
  • Glutathione
  • Cyclic GMP
  • potassium ferricyanide
  • Acetylcysteine