Rodent models of allergic rhinitis: Relevance to human pathophysiology

Wagner, James G.; Harkema, Jack R.

doi:10.1007/s11882-007-0011-5

Cited by 24 publications

(12 citation statements)

References 48 publications

(47 reference statements)

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“…To further elucidate the relationship between rhinitis and asthma and to better understand the pathophysiology of generalized airway inflammation, detailed study of a relevant large animal model that demonstrates concurrent upper and lower airway pathology is warranted [22]. Features that define asthma in humans, including eosinophilic bronchial inflammation, spontaneous and reversible bronchoconstriction, smooth muscle hypertrophy, and mucus gland hyperplasia, are also hallmark features of naturally occurring asthma in cats [23,24,25].…”

Section: Introductionmentioning

confidence: 99%

Histopathologic and Morphometric Evaluation of the Nasal and Pulmonary Airways of Cats with Experimentally Induced Asthma

Venema

Williams²,

Gershwin

et al. 2012

Int Arch Allergy Immunol

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Background: Allergic rhinitis frequently occurs as a comorbid condition in asthmatic people, suggesting that the upper and lower airways may be immunologically linked. Our research group has developed an experimental aeroallergen model of asthma in cats. We hypothesized that aeroallergen sensitization and challenge would induce morphologic changes in the nasal airways of cats that mimic those observed in the bronchial airways. Methods: Five mixed breed cats were sensitized to Bermuda grass allergen and then serially challenged with aerosolized Bermuda grass allergen to induce an asthmatic phenotype. Four control cats were similarly treated with saline vehicle. Nasal tissues and lungs were processed for histopathological and morphometric analyses. Results: Eosinophilic inflammation, epithelial hypertrophy and mucous cell metaplasia were observed along the pulmonary axial airway mucosa of allergen-sensitized (asthmatic) cats. Mild eosinophilic inflammation was observed in the nasal airways of asthmatic cats. This alteration was confined primarily to the anterior nasal cavity, resulting in an increase in tissue eosinophils at this site compared to controls (p < 0.05). A marked increase in tissue mast cells was observed throughout all regions of the nasal airways of asthmatic cats compared to control cats (p < 0.05). There was no difference in intraepithelial mucosubstances between the nasal airways of controls and asthmatic cats. There was no correlation between upper and lower airway eosinophils or mast cells. Conclusion: Cats with experimentally induced asthma exhibit morphologic changes in the nasal airways that are distinct from the alterations observed in the lungs. These results are similar to those observed in people with comorbid asthma and allergic rhinitis.

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Section: Introductionmentioning

confidence: 99%

Histopathologic and Morphometric Evaluation of the Nasal and Pulmonary Airways of Cats with Experimentally Induced Asthma

Venema

Williams²,

Gershwin

et al. 2012

Int Arch Allergy Immunol

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“…The rodent nose is different from humans in both anatomy and histology. More than 50% of the nasal cavity surface of rodents is lined by olfactory epithelium (44). Hence, it is likely that a fair amount of the 99m Tc-SC particles delivered into the mouse nose will be deposited on olfactory epithelial cells initially.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive real-time measurement of nasal mucociliary clearance in mice by pinhole gamma scintigraphy

Hua

Zeman

Zhou³

et al. 2010

Journal of Applied Physiology

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. Noninvasive real-time measurement of nasal mucociliary clearance in mice by pinhole gamma scintigraphy. J Appl Physiol 108: 189 -196, 2010. First published October 1, 2009 doi:10.1152/japplphysiol.00669.2009 is the key defense mechanism in the upper airways, as the removal of debris-laden mucus in the sinuses completely depends on MCC. So far, how the nasal MCC is regulated remains unknown. Recently, mice deficient in genes encoding the components of MCC apparatus have been generated, which will allow investigators to conduct more in-depth nasal MCC studies. However, the methodology necessary to comprehensively evaluate the nasal MCC in this species is not well established. We therefore developed a novel method to measure nasal MCC in live mice using pinhole gamma camera. Insoluble radiolabeled particles were delivered into the noses of lightly anesthetized mice. The nasal clearance of these particles was measured continuously in a real-time manner. The effect of three different anestheticsavertin, pentobarbital, and isoflurane-on nasal MCC was also determined. In mice anesthetized by 1.1% isoflurane, radiolabeled particles were immediately moved into the oropharynx, which was significantly accelerated by the treatment of hypertonic but not isotonic saline. According to the clearance rate, the mouse nasal MCC presented two distinct phases: a rapid phase and a slow phase. In addition, we found that isoflurane had a very small inhibitory effect on nasal MCC vs. both avertin and pentobarbital. This was further supported by its dose response. Collectively, we have developed a noninvasive method to monitor the real-time nasal MCC in live mice under physiological conditions. It provides more comprehensive evaluation on nasal MCC rather than assessing a single component of the MCC apparatus in isolation.anesthesia; isoflurane; avertin; pentobarbital; hypertonic saline MUCOCILIARY CLEARANCE (MCC) is an important innate defense mechanism by which both upper and lower airways cleanse their surface of inhaled pollutants, allergens, pathogens, and mucus secreted by goblet cells and submucosal glands. This protective mechanism is especially important in the upper airways and sinuses, as the removal of debris-laden mucus in the sinuses completely depends on MCC, whereas in the lower airways MCC can be compensated for by other mechanisms such as coughing (43). This hypothesis is further supported by the observations that mice with primary ciliary dyskinesia (PCD) only exhibit inflammation in the nose and sinuses but not in the lower airways and lungs; and that sinonasal symptoms usually emerge in the early stage of PCD patients (6,26,28,32,45). These observations have led to the theory that impaired MCC in the nose and sinuses is the central pathophysiological process in the pathogenesis of chronic rhinosinusitis (CRS), a disease that currently affects more than 12% of Americans more than 18 years old (35). The major purpose of diverse therapeutic strategies for CRS patients is to improve and restore their sinonasal MCC fun...

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“…Currently, multiple animal models have been developed, not only for the study of asthma but also for other allergic diseases such as atopic dermatitis [ 3 ], allergic conjunctivitis [ 4 ], food allergy , anaphylaxis [ 5 ], and allergic rhinitis [ 6 ]. These mouse models are important to elucidate the pathophysiological mechanisms of asthma, as well as to evaluate both safety and effi cacy of therapies in preclinical phase, before starting clinical phases in humans.…”

Section: Introductionmentioning

confidence: 99%

Review of Mouse Models Applied to the Study of Asthma

Garcia

Marcos-Vadillo

2016

Methods in Molecular Biology

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The diversity of asthma phenotypes increases its complexity. Animal models represent a useful tool to elucidate the pathophysiological mechanisms involved in both allergic and nonallergic asthma, as well as to identify potential targets for the development of new treatments. Among all available animal models, mice offer significant advantages for the study of asthma. In this chapter, the applications of mouse models to the study of asthma will be reviewed.

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Rodent models of allergic rhinitis: Relevance to human pathophysiology

Cited by 24 publications

References 48 publications

Histopathologic and Morphometric Evaluation of the Nasal and Pulmonary Airways of Cats with Experimentally Induced Asthma

Histopathologic and Morphometric Evaluation of the Nasal and Pulmonary Airways of Cats with Experimentally Induced Asthma

Noninvasive real-time measurement of nasal mucociliary clearance in mice by pinhole gamma scintigraphy

Review of Mouse Models Applied to the Study of Asthma

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