The Temporal Evolution of Airways Hyperresponsiveness and Inflammation

Riesenfeld, Erik; Allen, Gilman B.; Bates, Jason H. T.; Poynter, Matthew E.; Wu, Michael; Aimiand, Steven; Lundblad, Lennart K. A.

doi:10.4172/2155-6121.s1-005

Cited by 28 publications

(53 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…OVA/OVA treatment resulted in a pan-pulmonary cellular inflammation in all mice, with participation of both eosinophils (MBP) and neutrophils (MPO). The relatively low number neutrophils relative to eosinophils in the lung of OVA/OVA-treated mice can be ascribed to our treatment protocol, as neutrophils preferentially infiltrate the lung shortly after a challenge (Ͻ24 h) and eosinophils later (43). For the same reason, our relatively extended challenge protocol (6 consecutive days) probably accounts for the observation that only the number of eosinophils corresponded with the functional and biochemical sequels of OVA/OVA treatment (Fig.…”

Section: Discussionmentioning

confidence: 91%

Ablation of Arg1 in hematopoietic cells improves respiratory function of lung parenchyma, but not that of larger airways or inflammation in asthmatic mice

Cloots

Sankaranarayanan

Theije

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Cloots RH, Sankaranarayanan S, de Theije CC, Poynter ME, Terwindt E, van Dijk P, Hakvoort TB, Lamers WH, Köhler SE. Ablation of Arg1 in hematopoietic cells improves respiratory function of lung parenchyma, but not that of larger airways or inflammation in asthmatic mice. Am J Physiol Lung Cell Mol Physiol 305: L364-L376, 2013. First published July 5, 2013; doi:10.1152/ajplung.00341.2012.-Asthma is a chronic inflammatory disease of the small airways, with airway hyperresponsiveness (AHR) and inflammation as hallmarks. Recent studies suggest a role for arginase in asthma pathogenesis, possibly because arginine is the substrate for both arginase and NO synthase and because NO modulates bronchial tone and inflammation. Our objective was to investigate the importance of increased pulmonary arginase 1 expression on methacholine-induced AHR and lung inflammation in a mouse model of allergic asthma. Arginase 1 expression in the lung was ablated by crossing Arg1 fl/fl with Tie2Cre tg/Ϫ mice. Mice were sensitized and then challenged with ovalbumin. Lung function was measured with the Flexivent. Adaptive changes in gene expression, chemokine and cytokine secretion, and lung histology were quantified with quantitative PCR, ELISA, and immunohistochemistry. Arg1 deficiency did not affect the allergic response in lungs and large-airway resistance, but it improved peripheral lung function (tissue elastance and resistance) and attenuated adaptive increases in mRNA expression of arginine-catabolizing enzymes Arg2 and Nos2, arginine transporters Slc7a1 and Slc7a7, chemokines Ccl2 and Ccl11, cytokines Tnfa and Ifng, mucus-associated epithelial markers Clca3 and Muc5ac, and lung content of IL-13 and CCL11. However, expression of Il4, Il5, Il10, and Il13 mRNA; lung content of IL-4, IL-5, IL-10, TNF-␣, and IFN-␥ protein; and lung pathology were not affected. Correlation analysis showed that Arg1 ablation disturbed the coordinated pulmonary response to ovalbumin challenges, suggesting arginine (metabolite) dependence of this response. Arg1 ablation in the lung improved peripheral lung function and affected arginine metabolism but had little effect on airway inflammation. airway hyperresponsiveness; arginine; inflammation ALLERGIC ASTHMA IS A CHRONIC inflammatory disorder of the lung that is characterized by a reversible limitation of the airflow due to an allergic reaction in the airways with the characteristics of a T H 2-predominant airway inflammation. The airway inflammation is initiated by the binding of inhaled allergens to complementary IgEs on IgE receptor-bearing cells. Upon activation, these cells release histamine, cytokines, and proteases, resulting in the activation of the inflammatory cascade with lung infiltration of eosinophils and mononuclear cells. Increased mucus production, mucosal edema, and a disproportionate smooth-muscle contraction lead to airway hyperresponsiveness (AHR). As a result of the recurring inflammation, airway remodeling develops as a consequence of fibrosis and airway wall thickening (2,3,6,36).Rec...

show abstract

Section: Discussionmentioning

confidence: 91%

Ablation of Arg1 in hematopoietic cells improves respiratory function of lung parenchyma, but not that of larger airways or inflammation in asthmatic mice

Cloots

Sankaranarayanan

Theije

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…Although R N was similarly elevated in Glrx1 2/2 animals, increases in tissue resistance and tissue elastance parameters, representing the peripheral airways, were significantly attenuated toward control values ( Figure 6A). Characteristic features of allergic airways disease include excess mucus production and goblet cell hyperplasia (11,14), which have been shown to contribute to airway closure and hyperresponsiveness (15,16). Analysis of the mucin gene, mucin-5AC (Muc5ac), revealed attenuated mRNA expression in the lungs of HDM-exposed Glrx 2/2 mice in comparison to WT mice ( Figure 6B).…”

Section: Assessment Of Hdm-induced Airway Hyperresponsiveness and Mucmentioning

confidence: 99%

“…technique using a computer-controlled small animal ventilator (FlexiVent; SCIREQ, Montreal, PQ, Canada), as previously described (11,12).…”

Section: Assessment Of Airway Hyperresponsivenessmentioning

confidence: 99%

Ablation of Glutaredoxin-1 Modulates House Dust Mite–Induced Allergic Airways Disease in Mice

Hoffman¹,

Qian²,

Nolin³

et al. 2016

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Protein S-glutathionylation (PSSG) is an oxidant-induced posttranslational modification of protein cysteines that impacts structure and function. The oxidoreductase glutaredoxin-1 (Glrx1) under physiological conditions catalyzes deglutathionylation and restores the protein thiol group. The involvement of Glrx1/PSSG in allergic inflammation induced by asthma-relevant allergens remains unknown. In the present study, we examined the impact of genetic ablation of Glrx1 in the pathogenesis of house dust mite (HDM)-induced allergic airways disease in mice. Wild-type (WT) or Glrx1 2/2 mice were instilled intranasally with HDM on 5 consecutive days for 3 weeks. As expected, overall PSSG was increased in Glrx1 2/2 HDM mice as compared with WT animals. Total cells in bronchoalveolar lavage fluid were similarly increased in HDMtreated WT and Glrx1 2/2 mice. However, in response to HDM, mice lacking Glrx1 demonstrated significantly more neutrophils and macrophages but fewer eosinophils as compared with HDM-exposed WT mice. mRNA expression of the Th2-associated cytokines IL-13 and IL-6, as well as mucin-5AC (Muc5ac), was significantly attenuated in Glrx1 2/2 HDM-treated mice. Conversely, mRNA expression of IFN-g and IL-17A was increased in Glrx1 2/2 HDM mice compared with WT littermates. Restimulation of singlecell suspensions isolated from lungs or spleens with HDM resulted in enhanced IL-17A and decreased IL-5 production in cells derived from inflamed Glrx1 2/2 mice compared with WT animals. Finally, HDM-induced tissue damping and elastance were significantly attenuated in Glrx1 2/2 mice compared with WT littermates. These results demonstrate that the Glrx1-PSSG axis plays a pivotal role in HDM-induced allergic airways disease in association with enhanced type 2 inflammation and restriction of IFN-g and IL-17A.Keywords: asthma; protein S-glutathionylation; IL-17A; IFN-g; neutrophils Clinical RelevanceThis study demonstrates that the protein S-glutathionylation (PSSG)-glutaredoxin redox axis controls the nature of adaptive immune and inflammatory responses in an experimental model of allergic airways disease in mice. This advances our understanding the role that oxidative processes play in allergic disease and provides a platform for targeting PSSG chemistry to combat allergic airways disease.

show abstract

“…It was believed that eosinophils are predominant in asthma, but also the role of neutrophils in asthma is accepted. It has been proved that the majority of the asthmatic patients are noneosinophilic, whereas a direct correlation was reported between neutrophils and severity of asthma [27][28][29][30]. Riesenfeld et al reported variations of phenotypes of AHR in mouse models and believed that a better in understanding of asthma in humans is needed as well.…”

Section: Measurement Diagnosis and Treatmentmentioning

confidence: 99%

Airway Hyperresponsiveness: An Unsung Clinical Manifestation

Vd¹

2016

J Allergy Ther

View full text Add to dashboard Cite

Airway Hyperresponsiveness (AHR) is one of the key features of asthma and chronic obstructive pulmonary disease (COPD), where the airway sensitivity is increased. The research suggested that there is a relation between inflammatory state and severity of hyperresponsiveness of the airway, though the causative agents and consequences are different in asthma and COPD. However, before estimating hyperresponsiveness, there is a need to understand the consequences of airway inflammation, which are different in asthma and COPD. Over the past decades, there was an increased interest in unfold the multidimensional link between airway inflammation and hyperresponsiveness. This raises the hope for the future in development of diagnosis and treatment options for AHR. This short note intends to summarize the clinical correlation between airway inflammation and hyperresponsiveness and the significance of measurement of hyperresponsiveness.

show abstract

The Temporal Evolution of Airways Hyperresponsiveness and Inflammation

Cited by 28 publications

References 43 publications

Ablation of Arg1 in hematopoietic cells improves respiratory function of lung parenchyma, but not that of larger airways or inflammation in asthmatic mice

Ablation of Arg1 in hematopoietic cells improves respiratory function of lung parenchyma, but not that of larger airways or inflammation in asthmatic mice

Ablation of Glutaredoxin-1 Modulates House Dust Mite–Induced Allergic Airways Disease in Mice

Airway Hyperresponsiveness: An Unsung Clinical Manifestation

Contact Info

Product

Resources

About