Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis

Moeller, Alexander; Horák, F.; Lane, Catherine; Knight, Darryl A.; Kicic, Anthony; Brennan, Siobhain; Franklin, Peter; Terpolilli, Jason; Wildhaber, Johannes H.; Stick, Stephen M.

doi:10.1136/thx.2005.054643

Cited by 44 publications

(36 citation statements)

References 42 publications

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“…This humming peak is absent in patients with chronic sinusitis and those with cystic fibrosis [91,95]. There is evidence, in both these conditions, to suggest this is secondary to decreased expression of iNOS, leading to decreased nitric oxide biosynthesis [79,84,85,96].…”

Section: Hypothesis 3: Nitric Oxide Is Trapped In the Obstructed Paramentioning

confidence: 90%

“…It has also been reported that patients with cystic fibrosis have reduced or absent iNOS expression in the airway epithelia [79,84,85]. A recent study comparing NOS2 and NOS3 mRNA expression (the genes for iNOS and eNOS, respectively) in the nasal mucosa of patients with PCD and secondary ciliary dyskinesia (SCD) found that there was no difference in NOS3 expression but lower levels of NOS2 expression in the PCD group.…”

Section: Decreased Expression Of Nos Isoenzymesmentioning

confidence: 99%

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Nitric oxide in primary ciliary dyskinesia

et al. 2012

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Nitric oxide is continually synthesised in the respiratory epithelium and is upregulated in response to infection or inflammation. Primary ciliary dyskinesia (PCD) is characterised by recurrent sinopulmonary infections due to impaired mucociliary clearance. Despite chronic infections, nasal nitric oxide in such patients is markedly reduced and is used as a screening test for this condition. These low levels were first described .15 yrs ago but the underlying mechanisms have yet to be fully elucidated. We review epithelial nitric oxide synthesis, release and measurement in the upper airways with particular reference to PCD. The key hypotheses that have been proposed to explain the low nitric oxide levels in this condition are explored and the potential benefits of augmenting airway nitric oxide levels are considered. Further work in these patients clarifying both whether the respiratory epithelium is able to biosynthesise normal levels of nitric oxide and the role played by abnormalities in the anatomy of the paranasal sinuses is essential. While nitric oxide augmentation is unlikely to be beneficial in common PCD phenotypes, it has potential in the treatment of secondary dyskinesias and may also improve treatment of bacterial infections, particularly where biofilms are implicated.

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Section: Hypothesis 3: Nitric Oxide Is Trapped In the Obstructed Paramentioning

confidence: 90%

Section: Decreased Expression Of Nos Isoenzymesmentioning

confidence: 99%

Nitric oxide in primary ciliary dyskinesia

et al. 2012

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“…The present authors have successfully used this technique to examine biochemical and functional differences in AECs from children with and without asthma [9,10], and inducible nitric oxide responses in young children and infants with CF [11]. However, the increased use of laryngeal mask airways (LMA) in paediatric anaesthesia has significantly decreased the number of children in which this technique is now applicable.…”

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confidence: 99%

Comparison of techniques for obtaining lower airway epithelial cells from children

McNamara¹,

Kicic²,

Sutanto³

et al. 2008

European Respiratory Journal

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Airway epithelial cells (AECs) are important in asthma as they are the first cells to encounter pathogens/allergens. In children, AECs can be obtained using a ''blind'' nonbronchoscopic technique through an endotracheal tube. However, due to the increasing use of laryngeal masks the number of children in whom this technique is applicable has become limited. Recently, the present authors began to use a portable ''bronchoscope-directed'' technique to sample AECs. The current study compares both techniques in both asthmatic and nonasthmatic children.A total of 81 children undergoing elective surgery, were grouped according to atopic status and respiratory symptoms. Cellular yield of blind and bronchoscope-directed brushings were compared and immunocytochemistry performed. AECs were cultured and cytokine analysis of culture supernatant undertaken.Both techniques were equally well-tolerated, with the only adverse effect being a cough in 10% of the subjects. The mean¡SD cell yield was higher in bronchoscope-directed than blind brushings (5.1¡2.4 versus 3.1¡1.4x10 6 cells). Immunocytochemistry confirmed an epithelial cell lineage. Culture supernatant cytokine concentrations were similar regardless of sampling technique with patterns preserved between asthmatic and healthy nonatopic phenotypes. Compared with blind brushing portable bronchoscope-directed brushing is well-tolerated, yields significantly more cells and is a potentially quick and useful technique for obtaining airway epithelial cells for research into childhood respiratory disease, specifically asthma.

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“…In the lungs of patients suffering from CF, epithelial cells fail to produce NO in response to pathogen invasion and bacterial LPS sensing [80,81]. Impaired NO production may be due to reduced NOS expression, including both iNOS [80,82,83] and possibly cNOS [84], as well as reduced availability of the NOS substrate L-arginine, possibly due to increased arginase activity in CF airways [85]. …”

mentioning

confidence: 99%

Nitric Oxide: A Key Mediator of Biofilm Dispersal with Applications in Infectious Diseases

Barraud¹,

Kelso²,

Rice

et al. 2014

CPD

215

196

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Studies of the biofilm life cycle can identify novel targets and strategies for improving biofilm control measures. Of particular interest are dispersal events, where a subpopulation of cells is released from the biofilm community to search out and colonize new surfaces. Recently, the simple gas and ubiquitous biological signaling molecule nitric oxide (NO) was identified as a key mediator of biofilm dispersal conserved across microbial species. Here, we review the role and mechanisms of NO mediating dispersal in bacterial biofilms, and its potential for novel therapeutics. In contrast to previous attempts using high dose NO aimed at killing pathogens, the use of low, non-toxic NO signals (picomolar to nanomolar range) to disperse biofilms represents an innovative and highly favourable approach to improve infectious disease treatments. Further, several NO-based technologies have been developed that offer a versatile range of solutions to control biofilms, including: (i) NO-generating compounds with short or long half-lives and safe or inert residues, (ii) novel compounds for the targeted delivery of NO to infectious biofilms during systemic treatments, and (iii) novel NO-releasing materials and surface coatings for the prevention and dispersal of biofilms. Overall the use of low levels of NO exploiting its signaling properties to induce dispersal represents an unprecedented and promising strategy for the control of biofilms in clinical and industrial contexts. AbstractStudies of the biofilm life cycle can identify novel targets and strategies for improving biofilm control measures. Of particular interest are dispersal events, where a subpopulation of cells is released from the biofilm community to search out and colonize new surfaces. Recently, the simple gas and ubiquitous biological signaling molecule nitric oxide (NO) was identified as a key mediator of biofilm dispersal conserved across microbial species. Here, we review the role and mechanisms of NO mediating dispersal in bacterial biofilms, and its potential for novel therapeutics. In contrast to previous attempts using high dose NO aimed at killing pathogens, the use of low, non-toxic NO signals (picomolar to nanomolar range) to disperse biofilms represents an innovative and highly favourable approach to improve infectious disease treatments. Further, several NO-based technologies have been developed that offer a versatile range of solutions to control biofilms, including: (i) NO-generating compounds with short or long half-lives and safe or inert residues, (ii) novel compounds for the targeted delivery of NO to infectious biofilms during systemic treatments, and (iii) novel NO-releasing materials and surface coatings for the prevention and dispersal of biofilms. Overall the use of low levels of NO exploiting its signaling properties to induce dispersal represents an unprecedented and promising strategy for the control of biofilms in clinical and industrial contexts. 3 Increased antimicrobial tolerance in biofilms is the basis for chronic infecti...

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Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis

Cited by 44 publications

References 42 publications

Nitric oxide in primary ciliary dyskinesia

Nitric oxide in primary ciliary dyskinesia

Comparison of techniques for obtaining lower airway epithelial cells from children

Nitric Oxide: A Key Mediator of Biofilm Dispersal with Applications in Infectious Diseases

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