Invasive and noninvasive methods for studying pulmonary function in mice

Glaab, Thomas; Taube, Christian; Braun, Armin; Mitzner, Wayne

doi:10.1186/1465-9921-8-63

Cited by 112 publications

(129 citation statements)

References 55 publications

(81 reference statements)

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“…Indeed, compliance is negatively affected by an increased deposition of collagen fibrils in the parenchyma but also by smooth muscle constriction and/or peripheral airway inhomogeneities. An increase in elastic fiber deposition will also contribute to a reduced compliance and to greater elastic recoil (elastance) (10). The situation is reversed in decorin-deficient mice, which show improper collagen deposition.…”

Section: Discussionmentioning

confidence: 93%

“…There were two probable causes for the observed decreased in lung compliance. The increased stiffness of the lungs could have resulted from the accumulation of fibrous tissue in the lungs and/or the buildup of fluid in the alveolar spaces (10). Indeed, we found that an increase in airway resistance in cav1 Ϫ/Ϫ mice derived from the thickening of the subepithelium basement membrane caused by an overabundance of collagen deposition (unpublished observations).…”

Section: Cav1mentioning

confidence: 86%

“…Measurement of lung mechanics. Dynamic compliance and elastance were measured using a flexiVent instrument (SCIREQ, Montréal, Québec, Canada; http://www.scireq.com/products/flexivent) as previously described (9,10) according to the manufacturer's instructions. Briefly, mice were weighed before anesthesia with ketamine (100 mg/kg ip) and xylazine (10 mg/kg ip).…”

Section: Methodsmentioning

confidence: 99%

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The role of caveolin-1 in pulmonary matrix remodeling and mechanical properties

Saux

Teeters

Miyasato

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Caveolin-1 (cav1) is a 22-kDa membrane protein essential to the formation of small invaginations in the plasma membrane, called caveolae. The cav1 gene is expressed primarily in adherent cells such as endothelial and smooth muscle cells and fibroblasts. Caveolae contain a variety of signaling receptors, and cav1 notably downregulates transforming growth factor (TGF)-β signal transduction. In pulmonary pathologies such as interstitial fibrosis or emphysema, altered mechanical properties of the lungs are often associated with abnormal ECM deposition. In this study, we examined the physiological functions and the deposition of ECM in cav1−/− mice at various ages (1–12 mo). Cav1−/− mice lack caveolae and by 3 mo of age have significant reduced lung compliance and increased elastance and airway resistance. Pulmonary extravasation of fluid, as part of the cav1−/− mouse phenotype, probably contributed to the alteration of compliance, which was compounded by a progressive increase in deposition of collagen fibrils in airways and parenchyma. We also found that the increased elastance was caused by abundant elastic fiber deposition primarily around airways in cav1−/− mice at least 3 mo old. These observed changes in the ECM composition probably also contribute to the increased airway resistance. The higher deposition of collagen and elastic fibers was associated with increased tropoelastin and col1α2 and col3α1 gene expression in lung tissues, which correlated tightly with increased TGF-β/Smad signal transduction. Our study illustrates that perturbation of cav1 function may contribute to several pulmonary pathologies as the result of the important role played by cav1, as part of the TGF-β signaling pathway, in the regulation of the pulmonary ECM.

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Section: Discussionmentioning

confidence: 93%

Section: Cav1mentioning

confidence: 86%

Section: Methodsmentioning

confidence: 99%

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The role of caveolin-1 in pulmonary matrix remodeling and mechanical properties

Saux

Teeters

Miyasato

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Invasive monitoring of lung function by R L and C dyn is the classical method for accurate and specific determination of pulmonary mechanics (31). However, this method does not enable the repeated measure of pulmonary function.…”

Section: Discussionmentioning

confidence: 99%

Role of the Serotonergic System in Reduced Pulmonary Function after Exposure to Methamphetamine

Wells¹,

Buford²,

Porter³

et al. 2010

Am J Respir Cell Mol Biol

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Although use of methamphetamine (MA) by smoking is the fastest growing method of administration, very limited data are available describing the effects of smoked MA. Using a murine inhalation exposure system, we explored the pulmonary effects of low-dose acute inhalation exposure to MA vapor (smoke). Inhalation of MA vapor resulted in transiently reduced pulmonary function, as measured by transpulmonary resistance, dynamic compliance, and whole-body plethysmography compared with unexposed control animals. These changes were associated with an approximately 34% reduction in serotonin (5-hydroxytryptamine [5-HT]) metabolism/ inactivation to 5-hydroxyindolacetic acid, and a nearly 40% reduction in monoamine oxidase (MAO)-A activity in the lung. Pretreatment of mice with a selective 5-HT reuptake inhibitor completely ablated the MA-induced changes in pulmonary function, confirming a key role for the 5-HT transporter (serotonin transporter [SERT]) and the serotonergic system in this effect. Immunofluorescent staining of mouse lung tissue confirmed high expression of SERT in airway epithelial cells. Using mouse airway epithelial cell line, LA-4, and purified human MAO-A, it was demonstrated that MA impedes 5-HT metabolism through direct inhibition of MAO-A activity in vitro.Together, these data demonstrate that low-dose exposure to MA results in reduced pulmonary function mediated via SERT and subsequent perturbation of 5-HT metabolism in the lung. This supports a role for the serotonergic system in MA-mediated pulmonary effects.

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“…were given as an adjuvant. The OVA challenge was performed using a head-out bodyplethysmograph [27]. The protocol is outlined in figure 1a.…”

Section: Methodsmentioning

confidence: 99%

Kinetics of Regulatory T Cells in the Ovalbumin Asthma Model in the Rat

Jurawitz

Lührmann²,

Tschernig³

et al. 2008

Int Arch Allergy Immunol

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Background: The kinetics of regulatory T cells (T_Reg) in allergic diseases such as asthma are only partly known. Methods: The asthma model in the Fischer rat with ovalbumin (OVA) sensitization and aerosol challenge was used. The relative and absolute numbers of leukocytes, lymphocytes and T_Reg subsets were determined by flow cytometry in the lung interstitium and draining bronchial lymph nodes at different time points after two challenges, and lung function was tested in parallel. Results: The progressive number of challenges resulted in increased relative and absolute numbers of lymphocytes and in particular of T_Reg. The T_Reg number was augmented with each aerosol challenge and was already significantly increased 6 h after the second challenge. The relative (%) and absolute numbers of CD4+ and CD8+ T_Reg and dendritic cells showed different kinetics after two challenges. The leukocyte numbers in the lung did not correlate with lung function. Conclusion: T_Reg increased surprisingly early after challenge in the lung tissue. Relative and absolute numbers of leukocyte subsets should always be calculated. The kinetics of different leukocyte subsets can only be determined when several time points are studied.

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Invasive and noninvasive methods for studying pulmonary function in mice

Cited by 112 publications

References 55 publications

The role of caveolin-1 in pulmonary matrix remodeling and mechanical properties

The role of caveolin-1 in pulmonary matrix remodeling and mechanical properties

Role of the Serotonergic System in Reduced Pulmonary Function after Exposure to Methamphetamine

Kinetics of Regulatory T Cells in the Ovalbumin Asthma Model in the Rat

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