Inhibition of eosinophil chemotaxis by chronic blockade of nitric oxide biosynthesis

Ferreira, Heloisa H.A.; Medeiros, Marta V.; Lima, Carmen S. P.; Flores, Carlos A.; Sannomiya, Paulina; Antunes, Edson; Nucci, Gilberto De

doi:10.1016/0014-2999(96)00379-2

Cited by 46 publications

(30 citation statements)

References 39 publications

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“…The elimination of RNS had no effect on airway eosinophilia in guinea pigs or mice. There have been several reports that nonspecific NOS inhibitors inhibited eosinophil accumulation in the airways and eosinophil activities [20,21]. In other studies, iNOS-specific inhibitor inhibited allergen-induced airway eosinophilia [22,23].…”

Section: Discussionmentioning

confidence: 95%

iNOS depletion completely diminishes reactive nitrogen-species formation after an allergic response

Koarai¹,

Ichinose²,

Sugiura³

et al. 2002

European Respiratory Journal

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Nitric oxide (NO) shows proinflammatory actions mainly via reactive nitrogen species (RNS) formation through superoxide-and peroxidase-dependent mechanisms. The purpose of this study was to examine the role of inducible NO synthase (iNOS) in RNS production, airway hyperresponsiveness, and inflammation after allergen challenge.Ovalbumin (OVA)-sensitised, iNOS-deficient and wild-type mice were used. RNS production was assessed by nitrotyrosine (NT) immunoreactivity in the airways. Airway inflammation and responsiveness were evaluated by eosinophil accumulation and methacholine (i.v.) challenge, respectively.In wild-type mice, OVA-inhalation challenge increased iNOS immunoreactivity in airway epithelial cells as well as iNOS protein measured by Western blotting. The total amounts of nitrite and nitrate in bronchoalveolar lavage (BAL) fluid were increased, and NT immunoreactivity was also observed abundantly in airway inflammatory cells. In iNOS-deficient mice, both iNOS expression and NT formation were completely abolished, and the total amounts of nitrite and nitrate in BAL fluid were significantly decreased. In contrast, OVA-induced airway eosinophil recruitment and hyperresponsiveness were observed almost equally in wild-type and iNOS-deficient mice.These data suggest that reactive nitrogen species production after allergic reaction occurs totally via inducible nitric oxide synthase-dependent pathways. Allergenmediated airway eosinophil recruitment and hyperresponsiveness appear to be independent of reactive nitrogen species production. Eur Respir J 2002; 20: 609-616.

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Section: Discussionmentioning

confidence: 95%

iNOS depletion completely diminishes reactive nitrogen-species formation after an allergic response

Koarai¹,

Ichinose²,

Sugiura³

et al. 2002

European Respiratory Journal

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“…Inflammatory cell chemotactic factors, including RANTES and IL-5, are likely to encounter high local concentrations of NO, superoxide, and peroxynitrite in inflammatory sites. Several studies have examined the effects of NO on neutrophil, monocyte, and eosinophil chemotaxis, [33][34][35][36][37][38] but few have examined the effects on chemotactic factors.…”

Section: Discussionmentioning

confidence: 99%

Effects of Reactive Oxygen and Nitrogen Metabolites on RANTES. and IL-5-Induced Eosinophil Chemotactic Activity in vitro

Sato

Simpson

Grisham

et al. 1999

The American Journal of Pathology

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“…In fact, from the data obtained in this study there would appear to be an excellent correlation between the dose of L-NAME required to inhibit edema and eosinophilia. NO has also been demonstrated to be chemotactic for a variety of cell types including eosinophils and may, therefore, play a role in the recruitment of eosinophils into the lung (Belenky et al, 1993;Ferreira et al, 1996). Additionally, NO has effects on T cell function in that it inhibits the proliferation of cloned Th-1 cells but not Th-2 cells (Taylor-Robinson et al, 1994).…”

Section: Role Of No In Airway Inflammation In Rats 1289mentioning

confidence: 99%

Pharmacological Assessment of the Nitric-Oxide Synthase Isoform Involved in Eosinophilic Inflammation in a Rat Model of Sephadex-Induced Airway Inflammation

Birrell

McCluskie²,

Haddad³

et al. 2002

J Pharmacol Exp Ther

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Excessive local production of nitric oxide (NO) has been suggested to play a role in rodent models of airway inflammation and in pulmonary diseases such as asthma. However, even given the plethora of data available including gene expression data, pharmacological data, and gene deletion studies in animal models, it is still not clear which nitric-oxide synthase (NOS) isoform is involved in eosinophilic airway inflammation. In this rat study, the nonselective NOS inhibitor L-NAME (N G -nitro-L-arginine methyl ester), but not a selective inducible NOS (iNOS) inhibitor 1400W (N-3-(aminomethyl)benzyl)acetamidine), impacted on Sephadex-induced inflammation by significantly inhibiting lung edema, eosinophil infiltration, tumor necrosis factor ␣, interleukin-13, and eotaxin levels in the lung tissue. Furthermore, iNOS gene expression was not induced following Sephadex administration, which confirms that iNOS does not play a role in this model. To demonstrate that this phenomenon was not restricted to this model of asthma, L-NAME, but not 1400W, was shown to reduce eosinophilia in an antigen-induced model. However, in contrast to the Sephadex model, there was an induction of iNOS gene expression after antigen challenge. In a model of aerosolized lipopolysaccharide-induced inflammation, where iNOS gene expression is increased, 1400W inhibited the increased neutrophilia. These data suggest that the compound has been administered using an appropriate dosing regimen for iNOS inhibition in the rat lung. In conclusion, it appears that constitutive, not inducible, NOS isoforms are important in NO production in models of allergic inflammation, which questions whether there is a role for iNOS inhibitors as therapy for the treatment of asthma.

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Inhibition of eosinophil chemotaxis by chronic blockade of nitric oxide biosynthesis

Cited by 46 publications

References 39 publications

iNOS depletion completely diminishes reactive nitrogen-species formation after an allergic response

iNOS depletion completely diminishes reactive nitrogen-species formation after an allergic response

Effects of Reactive Oxygen and Nitrogen Metabolites on RANTES. and IL-5-Induced Eosinophil Chemotactic Activity in vitro

Pharmacological Assessment of the Nitric-Oxide Synthase Isoform Involved in Eosinophilic Inflammation in a Rat Model of Sephadex-Induced Airway Inflammation

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