Rat models of asthma and chronic obstructive lung disease

Martin, James G.; Tamaoka, Meiyo

doi:10.1016/j.pupt.2005.10.005

Cited by 47 publications

(36 citation statements)

References 75 publications

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“…It is known that rat develop both, immediate and late asthmatic responses after allergen challenge or after nonspecific challenge [12]. In sensitized rat in response to allergen challenge both, CD4+ and CD8+ cells are activated and they express Th2 cytokines [13]. Nevertheless, rat is a weak bronchoconstrictor and more agonist is necessary to produce the airways narrowing similar to guinea pigs [14].…”

Section: Discussionmentioning

confidence: 99%

“…In patients with bronchial asthma, there is only one available study showing that serum kynurenine was increased [17]. Typically OVA sensitization and challenge leads to Th2 phenotype generation [13], and in turn Th2 cytokines are released, mainly IL-4 and IL-13. It is known that both of these cytokines suppress indolamine 2,3 dioxygenase activity [18], which might result in the decrease in kynurenine generation or at least in the unchanged level in asthmatic subjects as compared to control groups.…”

Section: Discussionmentioning

confidence: 99%

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The concentration of kynurenine in rat model of asthma.

Kucharewicz

Kasacka²,

Pawlak³

et al. 2008

Folia Histochem Cytobiol.

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Asthma is a chronic inflammatory disease that involves the immune system activation. Evidence is accumulating about the role of kynurenine pathway in the immune system regulation. The kynurenine pathway includes several metabolites of tryptophan, among others kynurenine (KYN). To study the immunological system regulation in asthma a simple and sensitive models of asthma are required. In the present study we induced rat model of asthma using ovalbumin (OVA) sensitization followed by challenge with OVA. The development of asthma has been confirmed by plasma total IgE measurement and the histological examination. The concentration of KYN has been determined in plasma, lungs and liver by highperformance liquid chromatography (HPLC). In OVA sensitized rats the concentration of total IgE was statistically significantly increased as compared to VEH sensitized control groups (437.6 ± 97.7 kU/l vs 159.2 ± 22.7 kU/l, respectively; p< 0.01). In asthmatic animals, the number of eosinophils, neutrophils and mast cells increased considerably, and epithelial lesion and the increase in airway epithelium goblet cells and edema of bronchial mucosa were present. We did not observe any significant changes in the concentration of KYN in plasma, lungs or liver between studied groups. In conclusion, the concentration of KYN remains unchanged in asthmatic animals as compared to control groups. Further studies using rat model of asthma are warranted to establish the role of kynurenine pathway regulation in asthma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The concentration of kynurenine in rat model of asthma.

Kucharewicz

Kasacka²,

Pawlak³

et al. 2008

Folia Histochem Cytobiol.

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“…Alterations in the connective tissue structure and composition of the airway wall, a process termed remodelling, has been documented in human asthmatic airways [71,73,202] and in animal models [203,204]. Such changes might result in alterations in the passive mechanical properties of the airway wall, leading to a change in the wall diameter at which its inward recoil is balanced by the outward pull of the parenchymal attachments.…”

Section: Effects Of Chronic Lung-volume Alteration and Smooth Muscle mentioning

confidence: 99%

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

An¹,

Bai²,

Bates³

et al. 2007

European Respiratory Journal

342

298

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Excessive airway obstruction is the cause of symptoms and abnormal lung function in asthma.As airway smooth muscle (ASM) is the effecter controlling airway calibre, it is suspected that dysfunction of ASM contributes to the pathophysiology of asthma. However, the precise role of ASM in the series of events leading to asthmatic symptoms is not clear. It is not certain whether, in asthma, there is a change in the intrinsic properties of ASM, a change in the structure and mechanical properties of the noncontractile components of the airway wall, or a change in the interdependence of the airway wall with the surrounding lung parenchyma. All these potential changes could result from acute or chronic airway inflammation and associated tissue repair and remodelling.Anti-inflammatory therapy, however, does not ''cure'' asthma, and airway hyperresponsiveness can persist in asthmatics, even in the absence of airway inflammation. This is perhaps because the therapy does not directly address a fundamental abnormality of asthma, that of exaggerated airway narrowing due to excessive shortening of ASM.In the present study, a central role for airway smooth muscle in the pathogenesis of airway hyperresponsiveness in asthma is explored.

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“…These species were initially selected because both have been used extensively as animal models (14,20) with which to explore airway reactivity. In view of the strainrelated differences in airway responses to agonists (19), we selected a mouse (BALB/c) and rat (Sprague-Dawley) strain with average airway responsiveness for the present study.…”

mentioning

confidence: 99%

The contribution of Ca²⁺ signaling and Ca²⁺ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice

Bai

Sanderson²

2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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Bai Y, Sanderson MJ. The contribution of Ca 2ϩ signaling and Ca 2ϩ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice. Am J Physiol Lung Cell Mol Physiol 296: L947-L958, 2009. First published April 3, 2009 doi:10.1152/ajplung.90288.2008.-To determine the relative contributions of Ca 2ϩ signaling and Ca 2ϩ sensitivity to the contractility of airway smooth muscle cells (SMCs), we compared the contractile responses of mouse and rat airways with the lung slice technique. Airway contraction was measured by monitoring changes in airway lumen area with phase-contrast microscopy, whereas changes in intracellular calcium concentration ([Ca 2ϩ ]i) of the SMCs were recorded with laser scanning microscopy. In mice and rats, methacholine (MCh) or serotonin induced concentration-dependent airway contraction and Ca 2ϩ oscillations in the SMCs. However, rat airways demonstrated greater contraction compared with mice, in response to agonist-induced Ca 2ϩ oscillations of a similar frequency. Because this indicates that rat airway SMCs have a higher Ca 2ϩ sensitivity compared with mice, we examined Ca 2ϩ sensitivity with Ca 2ϩ -permeabilized airway SMCs in which the [Ca 2ϩ ]i was experimentally controlled. In the absence of agonists, high [Ca 2ϩ ]i induced a sustained contraction in rat airways but only a transient contraction in mouse airways. This sustained contraction of rat airways was relaxed by Y-23672, a Rho kinase inhibitor, but not affected by GF-109203X, a PKC inhibitor. The subsequent exposure of Ca 2ϩ -permeabilized airway SMCs, with high [Ca 2ϩ ]i, to MCh elicited a further contraction of rat airways and initiated a sustained contraction of mouse airways, without changing the [Ca 2ϩ ]i of the SMCs. Collectively, these results indicate that airway SMCs of rats have a substantially higher innate Ca 2ϩ sensitivity than mice and that this strongly influences the transduction of the frequency of Ca 2ϩ oscillations into the contractility of airway SMCs. lung slices; Ca 2ϩ oscillations; confocal microscopy; asthma; hyperresponsiveness ASTHMA IS CHARACTERIZED BY airway inflammation and airway hyperresponsiveness to nonspecific stimulation. Although airway inflammation is known to result in airway remodeling, airway hyperresponsiveness occurs in the early stages of asthma when no obvious airway remodeling is discernable. Consequently, the fundamental mechanism leading to the excessive contraction of airway smooth muscle cells (SMCs) remains unknown. A straightforward hypothesis is that the innate contractility of the SMCs has been enhanced in asthmatic airways. However, the experimental evidence addressing the contractile responses of asthmatic SMCs in vitro is inconsistent. Increased (4, 6, 18, 21), normal (4, 5, 10, 34), and even reduced (12, 33, 37) airway constriction has been reported in human asthmatic or animal airways. These discrepancies may also result from the different protocols, methods, and parameters used to evaluate SMCs contraction.To determine whether the cont...

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Rat models of asthma and chronic obstructive lung disease

Cited by 47 publications

References 75 publications

The concentration of kynurenine in rat model of asthma.

The concentration of kynurenine in rat model of asthma.

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

The contribution of Ca²⁺ signaling and Ca²⁺ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice

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Rat models of asthma and chronic obstructive lung disease

Cited by 47 publications

References 75 publications

The concentration of kynurenine in rat model of asthma.

The concentration of kynurenine in rat model of asthma.

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

The contribution of Ca2+ signaling and Ca2+ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice

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The contribution of Ca²⁺ signaling and Ca²⁺ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice