Cystic fibrosis lung disease: The role of nitric oxide

Grasemann, Hartmut; Ratjen, Félix

doi:10.1002/(sici)1099-0496(199912)28:6<442::aid-ppul10>3.0.co;2-4

Cited by 46 publications

(33 citation statements)

References 59 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is now widely accepted that NO formation in the upper and lower airways is decreased in CF [1,2,21,22], and the results from the present study confirm these findings. The reasons for decreased NO formation in CF are not completely understood, but studies in mouse models and in patients with CF have found that the expression of the inducible isoform of NO synthases (NOS2) is decreased or absent in CF airways [3,4,22].…”

Section: Discussionsupporting

confidence: 89%

“…The fraction of exhaled NO (eNO) has been found to be reduced in patients with cystic fibrosis (CF) compared to healthy individuals [1]. The mechanisms that lead to low airway NO in CF are not completely understood but may include mechanical retention of NO in airway secretions, conversion of NO to metabolites, and consumption of NO by denitrifying bacteria [2]. Whilst limited evidence would support all of these concepts, there is also evidence for reduced enzymatic formation of NO in CF, whereby blood or tissue levels of L-arginine may become rate limiting for NO synthesis [3,4].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Oral L-arginine supplementation in cystic fibrosis patients: a placebo-controlled study

Grasemann

Grasemann²,

Kurtz³

et al. 2005

Eur Respir J

View full text Add to dashboard Cite

Exhaled nitric oxide (eNO) is decreased in cystic fibrosis (CF). The effect of oral Larginine, the precursor of enzymatic nitric oxide (NO) formation, on airway NO in patients with CF was studied.In a pilot study, oral L-arginine was given in a single dose of 200 mg?kg -1 body weight to eight healthy controls and eight CF patients. Subsequently, the same L-arginine dose was given to 10 patients with CF (five females) t.i.d. for 6 weeks in a randomised double-blind placebo-controlled crossover study.A single dose of oral L-arginine resulted in a 5.5-fold increase of L-arginine in plasma and a 1.3-fold increase of L-arginine in sputum after 2 h. Maximum eNO, within 3 h of L-arginine intake, increased significantly in both CF patients (5.4¡2.1 ppb versus 8.3¡3.5 ppb) and controls (18.0¡8.1 ppb versus 26.4¡12.3 ppb). Supplementation of L-arginine for 6 weeks resulted in a sustained increase in eNO compared to placebo (9.7¡5.7 ppb versus 6.3¡3.1 ppb). An effect of L-arginine supplementation on forced expiratory volume in one second was not observed.These data indicate that airway nitric oxide formation in cystic fibrosis patients can be augmented with oral L-arginine supplementation.

show abstract

Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Oral L-arginine supplementation in cystic fibrosis patients: a placebo-controlled study

Grasemann

Grasemann²,

Kurtz³

et al. 2005

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…We found that the NOS inhibitor L-AME inhibited the response to both PCA and pyocyanin. In this respect, phenazine-dependent superoxide formation might scavenge NO and thus prevent its anti-inflammatory effects (37). In addition, we cannot rule out the possibility that the product of superoxide and NO, peroxynitrite, might directly contribute to phenazine-dependent increases in IL-8 and ICAM-1 expression.…”

Section: Discussionmentioning

confidence: 94%

Pyocyanin and Its Precursor Phenazine-1-Carboxylic Acid Increase IL-8 and Intercellular Adhesion Molecule-1 Expression in Human Airway Epithelial Cells by Oxidant-Dependent Mechanisms

Look¹,

Stoll²,

Romig³

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Pseudomonas aeruginosa secretes numerous factors that alter host cell function and may contribute to disease pathogenesis. Among recognized virulence factors is the redox-active phenazine pyocyanin. We have recently demonstrated that the precursor for pyocyanin, phenazine-1-carboxylic acid (PCA), increases oxidant formation and alters gene expression in human airway epithelial cells. We report in this work that PCA and pyocyanin increase expression of ICAM-1 both in vivo and in vitro. Moreover, phenazines enhanced cytokine-dependent increases in IL-8 and ICAM-1. Antioxidant intervention studies indicated both similarities and differences between PCA and pyocyanin. The thiol antioxidant N-acetyl cysteine, extracellular catalase, and inducible NO synthase inhibitors inhibited ICAM-1 and IL-8 increases in response to both phenazines. However, pyocyanin was significantly more sensitive to N-acetylcysteine inhibition. Interestingly, hydroxyl radical scavengers inhibited the response to pyocyanin, but not to PCA. These studies suggest that P. aeruginosa phenazines coordinately up-regulate chemokines (IL-8) and adhesion molecules (ICAM-1) by mechanisms that are, at least in part, oxidant dependent. However, results indicate that the mechanisms by which PCA and pyocyanin exert their effects are not identical, and not all antioxidant interventions are equally effective in inhibiting phenazine-mediated proinflammatory effects.

show abstract

“…Although plateau NO concentration (C NO ,plat ) in patients with cystic fibrosis (CF), a congenital lung disease marked by inflammation, has been reported to be decreased (7)(8)(9), it has also been reported to be unchanged (5,6,(10)(11)(12)(13) when compared with healthy control subjects. These paradoxical results for CF can be explained potentially by both real alterations in the underlying physiology due to differences in disease penetration, duration of disease, types of colonizing organisms, and the coexistence of atopy or asthma, as well as differences in the experimental protocol (e.g., variation in exhalation flow rate) (14,15).…”

mentioning

confidence: 99%

Flow-independent Nitric Oxide Exchange Parameters in Cystic Fibrosis

Shin

Rose-Gottron

Sufi

et al. 2002

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Exhaled nitric oxide (NO) remains a promising noninvasive index for monitoring inflammatory lung diseases; however, the plateau concentration (C NO,plat ) is nonspecific and requires a constant exhalation flow rate. We utilized a new technique that employs a variable flow rate to estimate key flow-independent parameters characteristic of NO exchange in a group (n ϭ 9) of 10 to 14 yr-old healthy children and children with cystic fibrosis (CF): maximum flux of NO from the airways (J NO,max , pl s

show abstract

Cystic fibrosis lung disease: The role of nitric oxide

Cited by 46 publications

References 59 publications

Oral L-arginine supplementation in cystic fibrosis patients: a placebo-controlled study

Oral L-arginine supplementation in cystic fibrosis patients: a placebo-controlled study

Pyocyanin and Its Precursor Phenazine-1-Carboxylic Acid Increase IL-8 and Intercellular Adhesion Molecule-1 Expression in Human Airway Epithelial Cells by Oxidant-Dependent Mechanisms

Flow-independent Nitric Oxide Exchange Parameters in Cystic Fibrosis

Contact Info

Product

Resources

About