Effects of Nitric Oxide on Chemotaxis and Endotoxin-Induced Interleukin-8 Production in Human Neutrophils

• Published in: The Journal of infectious diseases 1998-01, Vol.177 (1), p.116-126
• Main Authors: Corriveau, Christiane C., Madara, Patricia J., Dervort, Alan L. Van, Tropea, Margaret M., Wesley, Robert A., Danner, Robert L.
• Format: Article
• Language: English
• Subjects: Acetylcysteine - pharmacology; Biological and medical sciences; Cells, Cultured; Chemotactic factors; Chemotaxis; Complement C5a - pharmacology; Cyclic GMP - metabolism; Dibutyryl Cyclic GMP - pharmacology; Dose-Response Relationship, Drug; Endothelial cells; Endothelium; Ferricyanides - pharmacology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glutathione - analogs & derivatives; Glutathione - pharmacology; Humans; Immunobiology; Interleukin-8 - metabolism; Interleukin-8 - pharmacology; Leukotriene B4 - pharmacology; Lipopolysaccharides - pharmacology; Major Articles; Messenger RNA; Molsidomine - analogs & derivatives; Molsidomine - pharmacology; Myeloid cells: ontogeny, maturation, markers, receptors; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophils; Neutrophils - metabolism; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; Nitroprusside - pharmacology; Nitroso Compounds - pharmacology; omega-N-Methylarginine - pharmacology; Oxides; Physiological regulation; Polynuclears; RNA, Messenger - metabolism; S-Nitrosoglutathione; Sodium; Up-Regulation; Viability
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/513829

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 (Nω-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. Upregulation 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.