Expression of nitric oxide synthases and in vitro migration of eosinophils from allergic rhinitis subjects

• Published in: European journal of pharmacology Vol. 442; no. 1; pp. 155 - 162
• Main Authors: Ferreira, Heloisa H.A., Lodo, Mônia L.S., Martins, Antonio R., Kandratavicius, Ludmyla, Salaroli, Antonio F., Conran, Nicola, Antunes, Edson, De Nucci, Gilberto
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 03.05.2002; Elsevier
• Subjects: 1400 W; Allergic diseases; Allergic rhinitis; Biological and medical sciences; Cell Movement - drug effects; Chemokine CCL11; Chemokines, CC - pharmacology; Chemotaxis; Chemotaxis - drug effects; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Eosinophil; Eosinophils - drug effects; Eosinophils - enzymology; Eosinophils - pathology; Eotaxin; Guanylate Cyclase - antagonists & inhibitors; Guanylate Cyclase - metabolism; Humans; Immunopathology; Isoenzymes - biosynthesis; Medical sciences; Molsidomine - analogs & derivatives; Molsidomine - pharmacology; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide (NO) synthase; Nitric Oxide - metabolism; Nitric Oxide Donors - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase Type II; Oxadiazoles - pharmacology; Quinoxalines - pharmacology; Respiratory and ent allergic diseases; Rhinitis, Allergic, Perennial - blood; Rhinitis, Allergic, Perennial - pathology; S-Nitroso-N-Acetylpenicillamine - pharmacology; Solubility; 1400 W; Nitric oxide (NO) synthase; Chemotaxis; Allergic rhinitis; Eosinophil; Eotaxin; Human; Immunopathology; Allergy; Nose disease; Healthy subject; Pathophysiology; Rhinitis; Enzyme; 3',5'-GMP; Gene expression; Nitric-oxide synthase; Nitric oxide; Interindividual comparison; ENT disease; Oxidoreductases
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)01507-8

The expression of nitric oxide (NO) synthases and the role of the NO cyclic GMP pathway on the migration of eosinophils from untreated patients with allergic rhinitis were investigated. Inducible NO synthase was strongly expressed in eosinophils from healthy individuals, but not in eosinophils from allergic rhinitis patients. The neuronal isoform was observed in eosinophils from each group studied, whereas no staining for the endothelial isoform was detected in either group. The chemotaxis to N-formyl-methionyl-leucyl-phenylalanine (fMLP, 5×10 −7 M) and eotaxin (100 ng/ml) was significantly potentiated in allergic rhinitis eosinophils. In both groups, N ω-nitro- l-arginine methyl ester ( l-NAME, 1.0 mM) or 1 H(1,2,4)-oxadiazolo(4,3,-a)quinoxalin-1-one (ODQ, 0.2 mM) markedly reduced the chemotaxis. The selective iNOS inhibitor N-(3-(aminomethyl)benzyl)acetamidine (1400 W, 0.1–1.0 mM) significantly reduced the chemotaxis of eosinophils from healthy but not from allergic rhinitis subjects. The inhibition by l-NAME was restored by 3-morpholinosydnonimine (SIN-1) and S-nitroso- N-acetyl-penicillamine, whereas the inhibition by ODQ was restored by dibutyryl cyclic GMP. In conclusion, both endothelial and inducible NO synthase isoforms are absent in allergic rhinitis eosinophils, suggesting that the NO cyclic GMP pathway in this cell type is maintained through the activity of a neuronal isoform.