Effects of nitric oxide on chemotaxis and endotoxin-induced interleukin-8 production in human neutrophils.
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.
Corriveau
C C
CC
Critical Care Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
Madara
P J
PJ
Van Dervort
A L
AL
Tropea
M M
MM
Wesley
R A
RA
Danner
R L
RL
D000111:Acetylcysteine / Q000494:pharmacology; D002478:Cells, Cultured; D002633:Chemotaxis; D015936:Complement C5a / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005292:Ferricyanides / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism* / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D026422:S-Nitrosoglutathione; D015854:Up-Regulation; D019323:omega-N-Methylarginine / Q000494:pharmacology
D005292:Ferricyanides; D016209:Interleukin-8; D008070:Lipopolysaccharides; D009603:Nitroso Compounds; D012333:RNA, Messenger; D009599:Nitroprusside; D007975:Leukotriene B4; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003995:Dibutyryl Cyclic GMP; D026422:S-Nitrosoglutathione; D009240:N-Formylmethionine Leucyl-Phenylalanine; C002385:linsidomine; D015936:Complement C5a; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D005978:Glutathione; D006152:Cyclic GMP; C028033:potassium ferricyanide; D000111:Acetylcysteine