Tidal midexpiratory flow as a measure of airway hyperresponsiveness in allergic mice

Glaab, Thomas; Daser, Angelika; Braun, Armin; Neuhaus-Steinmetz, Ulrich; Fabel, H; Alarie, Yves; Renz, Harald

doi:10.1152/ajplung.2001.280.3.l565

Cited by 87 publications

(89 citation statements)

References 27 publications

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“…Doubling doses of nebulized methacholine aerosols (0.75-25 mg/ml) were delivered to the head compartment of the plethysmograph, and bronchoconstriction data were gathered as running 1 s means of the airflow at the 50% point in the expiratory cycle (Flow@50%TVe1). This parameter accurately reflects bronchiolar constriction, as opposed to alveolar constriction or airway occlusion (23), and has been shown to correlate well with invasive measurements of AHR (24,25).…”

Section: Airway Hyperresponsivenessmentioning

confidence: 85%

Induction of Prolonged Asthma Tolerance by IL-10–Differentiated Dendritic Cells: Differential Impact on Airway Hyperresponsiveness and the Th2 Immunoinflammatory Response

Nayyar

Dawicki

Huang

et al. 2012

The Journal of Immunology

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IL-10–differentiated dendritic cells (DC10s) can prevent allergen sensitization and reverse the asthma phenotype in mice with established disease. However, little is known about the time-frames over which this tolerance is effective. We report that at 2 wk after i.p. or transtracheal delivery of 1 × 106 OVA-, but not house dust mite- presenting, DC10s to OVA-asthmatic mice, significant diminution of airway hyperresponsiveness (AHR) was first apparent, whereas AHR was abrogated between 3 and 10 wk posttreatment. At 13 wk, AHR returned to pretreatment levels but could again be reversed by DC10 retreatment. The impact of a single DC10 treatment on airway eosinophil and Th2 cytokine responses to recall OVA challenge, and on OVA-specific IgE/IgG1 responses, was substantial at 3 wk posttreatment, but progressively increased thereafter, such that at 8 mo, airway eosinophil and Th2 responses to recall allergen challenge remained ∼85–95% suppressed relative to saline-treated asthmatic mice. Four biweekly DC10 treatments, whether transtracheal or i.p., reduced all asthma parameters to near background by 8 wk, whereas s.c. DC10 treatments did not affect AHR but did reduce the airway Th2 responses (i.v. DC10 had no discernible effects). Repeated challenge of the DC10-treated mice with aerosolized OVA (100 μg/ml) did not reverse tolerance, but treatment with the indoleamine-2,3-dioxygenase antagonist 1-methyltryptophan or neutralizing anti–IL-10R from days 12 to 21 after DC10 therapy partially reversed tolerance (Th2 cytokine responses, but not AHR). These findings indicate that DC10-induced Th2 tolerance in asthmatic animals is long lived, but that DC10s employ distinct mechanisms to affect AHR versus Th2 immunoinflammatory parameters.

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Section: Airway Hyperresponsivenessmentioning

confidence: 85%

Induction of Prolonged Asthma Tolerance by IL-10–Differentiated Dendritic Cells: Differential Impact on Airway Hyperresponsiveness and the Th2 Immunoinflammatory Response

Nayyar

Dawicki

Huang

et al. 2012

The Journal of Immunology

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“…This conflicting result may be related to the marked variation among the used models with respect to the background strains of the animals, [26][27][28] the variety of sensitization and challenge protocols used, and the different readouts used to assess the airway responsiveness. 29,30 It is of interest to note that in naive animals lacking the tachykinin NK 1 receptor, an increased responsiveness to intravenous carbachol was observed. This observation corroborates the fact that mice with a targeted deletion of the tachykinin I gene (mice lacking substance P) are hyperresponsive to intravenous methacholine.…”

Section: Discussionmentioning

confidence: 99%

The role of the tachykinin NK1 receptor in airway changes in a mouse model of allergic asthma

Swert

Tournoy

Joos

et al. 2004

Journal of Allergy and Clinical Immunology

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Background: Tachykinins are present in sensory nerves and in nonneuronal cells like macrophages. Human data suggest a role for these peptides in asthma, but the exact role of tachykinins and their receptors in allergic airway inflammation is still a matter of debate. Objective: The aim of this study was to determine the role of the tachykinin NK 1 receptor in allergic airway responses in a mouse model. Methods: Tachykinin NK 1 receptor wild-type and knockout animals were sensitized intraperitoneally to ovalbumin and subsequently exposed from days 14 to 21 to aerosolized ovalbumin (1%). On day 22, the immunologic and histologic changes were evaluated, and lung function measurements were performed. Results: Mice lacking the tachykinin NK 1 receptor and their wild-type litter mates developed inflammatory cell infiltrates in the airways and ovalbumin-specific IgE on sensitization and exposure to ovalbumin compared with saline-exposed controls. No differences were detected between wild-type and knockout mice. The substance P content of alveolar macrophages was not influenced by ovalbumin or by the lack of the NK 1 receptor. Ovalbumin-induced hyperresponsiveness was not observed, but at baseline, the knockout mice were more reactive despite similar morphology. Ovalbumin induced more goblet cell hyperplasia in wild-type animals compared with knockout animals. No differences in airway wall thickness were observed. Conclusion: These data suggest that tachykinin NK 1 receptors do not affect allergic airway inflammation or endogenous substance P content of alveolar macrophages but influence baseline responsiveness and promote features of remodeling such as goblet cell

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“…The mid-expiratory airflow of bronchial responsiveness to b-methacholine was measured as described previously [25].…”

Section: Airway Reactivitymentioning

confidence: 99%

Clara cells drive eosinophil accumulation in allergic asthma

Sonar

Ehmke²,

Marsh³

et al. 2011

European Respiratory Journal

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Development of allergic asthma is a complex process involving immune, neuronal and tissue cells. In the lung, Clara cells represent a major part of the ''immunomodulatory barrier'' of the airway epithelium.To understand the contribution of these cells to the inflammatory outcome of asthma, disease development was assessed using an adjuvant-free ovalbumin model. Mice were sensitised with subcutaneous injections of 10 mg endotoxin-free ovalbumin in conjunction with naphthaleneinduced Clara cell depletion.Clara epithelial cell depletion in the lung strongly reduced eosinophil influx, which correlated with decreased eotaxin levels and, moreover, diminished the T-helper cell type 2 inflammatory response, including interleukin (IL)-4, IL-5 and IL-13. In contrast, airway hyperresponsiveness was increased. Further investigation revealed Clara cells as the principal source of eotaxin in the lung.These findings are the first to show that Clara airway epithelial cells substantially contribute to the infiltration of eotaxin-responsive CCR3+ immune cells and augment the allergic immune response in the lung. The present study identifies Clara cells as a potential therapeutic target in inflammatory lung diseases such as allergic asthma.

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Tidal midexpiratory flow as a measure of airway hyperresponsiveness in allergic mice

Cited by 87 publications

References 27 publications

Induction of Prolonged Asthma Tolerance by IL-10–Differentiated Dendritic Cells: Differential Impact on Airway Hyperresponsiveness and the Th2 Immunoinflammatory Response

Induction of Prolonged Asthma Tolerance by IL-10–Differentiated Dendritic Cells: Differential Impact on Airway Hyperresponsiveness and the Th2 Immunoinflammatory Response

The role of the tachykinin NK1 receptor in airway changes in a mouse model of allergic asthma

Clara cells drive eosinophil accumulation in allergic asthma

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