Local nitric oxide levels reflect the degree of allergic airway inflammation after segmental allergen challenge in asthmatics

Nitric Oxide ◽  
2005 ◽  
Vol 13 (2) ◽  
pp. 125-133 ◽  
Author(s):  
Veit J. Erpenbeck ◽  
Rudolf A. Jörres ◽  
Marc Discher ◽  
Harald Krentel ◽  
Dimitrios Tsikas ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Airway Inflammation ◽  
Allergen Challenge ◽  
Allergic Airway Inflammation ◽  
Segmental Allergen Challenge

Exhaled nitric oxide estimation by a simple and efficient noninvasive technique and its utility as a marker of airway inflammation in mice

2009 ◽  
Vol 107 (1) ◽  
pp. 295-301 ◽  
Author(s):  
Tanveer Ahmad ◽  
Ulaganathan Mabalirajan ◽  
Duraisamy Arul Joseph ◽  
Lokesh Makhija ◽  
Vijay Pal Singh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Airway Inflammation ◽  
Airway Remodeling ◽  
Allergen Challenge ◽  
Allergic Airway Inflammation ◽  
Ambient Air ◽  
Exhaled Nitric Oxide ◽  
Noninvasive Technique ◽  
Modified Method ◽  
Chronic Models

Allergic airway inflammation (AI) is commonly associated with enhanced exhaled nitric oxide (ENO) in both humans and mice. Since mouse models are being used to understand various mechanisms of asthma, a noninvasive, simple, and reproducible method to determine ENO in mice is required for serial nonterminal assessment that can be used independent of environmental situations in which the ambient air contains substantial amounts of NO as a contaminant. The aim of this study was to noninvasively measure ENO in individual mice and to test its utility as a marker of AI in different models of allergic AI. We modified the existing ENO measuring methods by incorporating flushing and washout steps that allowed simple but reliable measurements under highly variable ambient NO conditions (1–100 ppb). This method was used to serially follow ENO in acute and chronic models of allergic AI in mice. ENO was reproducibly measured by this modified method and was positively correlated to AI in both acute and chronic models of asthma but was not independently related to airway remodeling. Resolution of AI and other related parameters in dexamethasone-treated mice resulted in reduction of ENO, further confirming this association. Restriction of allergen challenge to pulmonary but not nasal airways was associated with a smaller increase in ENO compared with allergen challenge to both. Hence, ENO can now be reliably measured in mice independent of ambient NO levels and is a valid biomarker for AI. However, nasal and pulmonary airways are likely to be independent sources of ENO, and any results must be interpreted as such.

Nitric oxide regulation of asthmatic airway inflammation with segmental allergen challenge☆☆☆

1999 ◽  
Vol 104 (6) ◽  
pp. 1174-1182 ◽  
Author(s):  
Mary Jane Thomassen ◽  
Baisakhi Raychaudhuri ◽  
Raed A. Dweik ◽  
Carol Farver ◽  
Lisa Buhrow ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Airway Inflammation ◽  
Allergen Challenge ◽  
Asthmatic Airway ◽  
Segmental Allergen Challenge

Plasma arginine metabolites reflect airway dysfunction in a murine model of allergic airway inflammation

2015 ◽  
Vol 118 (10) ◽  
pp. 1229-1233 ◽  
Author(s):  
Jeremy A. Scott ◽  
Michelle L. North ◽  
Mahrouk Rafii ◽  
Hailu Huang ◽  
Paul Pencharz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Airway Inflammation ◽  
Plasma Concentrations ◽  
Allergic Airway Inflammation ◽  
Airway Responsiveness ◽  
Arginase Activity ◽  
Therapeutic Interventions ◽  
Oxide Synthase

l-Arginine metabolism is important in the maintenance of airway tone. Shift of metabolism from the nitric oxide synthase to arginase pathways contributes to the increased airway responsiveness in asthma. We tested the hypothesis that systemic levels of l-arginine metabolites are biomarkers reflective of airway dysfunction. We used a mouse model of acute allergic airway inflammation to OVA that manifests with significant airway hyperresponsiveness to methacholine. To determine tissue arginase activity in vivo, the isotopic enrichment of an infused l-arginine stable isotope and its product amino acid l-ornithine were measured in lung and airway homogenates using liquid chromatography-tandem mass spectrometry. Tissue and plasma concentrations of other l-arginine metabolites, including l-citrulline and symmetric and asymmetric dimethylarginine, were measured and correlated with lung arginase activity and methacholine responsiveness of the airways. The effectiveness of intratracheal instillation of an arginase inhibitor (boronoethylcysteine) on pulmonary arginase activity and circulating concentrations of l-arginine metabolites was also studied. We demonstrate that 1) plasma indexes of l-arginine bioavailability and impairment of nitric oxide synthase function correlate with airway responsiveness to methacholine; 2) plasma levels of l-ornithine predict in vivo pulmonary arginase activity and airway function; and 3) acute arginase inhibition reduces in vivo pulmonary arginase activity to control levels and normalizes plasma l-ornithine, but not l-arginine, bioavailability in this model. We conclude that plasma l-ornithine may be useful as a systemic biomarker to predict responses to therapeutic interventions targeting airway arginase in asthma.

scholarly journals CTLA4-Ig inhibits allergic airway inflammation by a novel CD28-independent, nitric oxide synthase-dependent mechanism

2010 ◽  
Vol 40 (7) ◽  
pp. 1985-1994 ◽  
Author(s):  
Christine M. Deppong ◽  
Amit Parulekar ◽  
Jonathan S. Boomer ◽  
Traci L. Bricker ◽  
Jonathan M. Green
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Oxide Synthase ◽  
Dependent Mechanism

Off-Line Fractional Exhaled Nitric Oxide Measurement Is Useful to Screen Allergic Airway Inflammation in an Adult Population

2007 ◽  
Vol 44 (10) ◽  
pp. 805-810 ◽  
Author(s):  
Junpei Saito ◽  
Suguru Sato ◽  
Hideki Hasunuma ◽  
Yasushi Ishimaru ◽  
Hiroshi Kanegae ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Airway Inflammation ◽  
Adult Population ◽  
Allergic Airway Inflammation ◽  
Exhaled Nitric Oxide ◽  
Fractional Exhaled Nitric Oxide

scholarly journals Specific Immunotherapy in a Murine Model of Grass Pollen (Phl p5b)-Induced Airway Inflammation

2021 ◽  
Vol 2 ◽  
Author(s):  
Matthias Stiehm ◽  
Marcus Peters
Keyword(s):  
Airway Inflammation ◽  
Murine Model ◽  
Grass Pollen ◽  
Specific Immunotherapy ◽  
Allergen Challenge ◽  
Allergic Airway Inflammation ◽  
Interleukin 5 ◽  
Grass Pollen Allergen ◽  
Adjuvant Effects

Background: The use of ovalbumin as a model allergen in murine models of allergic asthma is controversially discussed since it is not an aeroallergen and sensitization can only be achieved by using strong Th2-inducing adjuvants. Therefore, in this study, a murine model of asthma has been established in which sensitization against the major grass pollen allergen Phl p5b was performed without using aluminum hydroxide (alum). We used this model for specific immunotherapy.Methods: Female, 5–6-week-old mice were sensitized by six subcutaneous (s.c.) injections of 20 μg Phl p5b followed by four provocations to induce allergic airway inflammation. For desensitization, 1 mg of Phl p5b was injected subcutaneously during allergen challenge for one to a maximum of four times. Three days after the last challenge, the allergic immune response was analyzed.Results: Sensitized and challenged animals showed a significant infiltration of eosinophils into the airways, and the production of interleukin-5 (IL-5) by in vitro re-stimulated splenocytes could be detected. Furthermore, hyper-responsiveness of the airways was verified by invasive measurement of airway resistance in methacholine-challenged animals. Desensitized animals showed a significant reduction of all parameters.Conclusion: In this study, a murine model of asthma has successfully been established by sensitization against the clinically relevant allergen Phl p5b without using alum. S.c. injection of allergen dose dependently led to desensitization of sensitized mice. We suggest that this model is useful to study adjuvant effects of immune modulatory substances on immunotherapy without the interference of alum.

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