Absence of cholinergic airway tone in normal BALB/c mice

Larcombe, Alexander N.; Zosky, Graeme R.; Bozanich, Elizabeth M.; Turner, Debra J.; Hantos, Zoltán; Sly, Peter D.

doi:10.1016/j.resp.2008.01.009

Cited by 10 publications

(8 citation statements)

References 41 publications

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“…Animal preparation (postexposure). Twenty-four hours after the last exposure, mice were prepared for lung function assessment as previously described (24).…”

Section: Methodsmentioning

confidence: 99%

“…TGV was then calculated using Boyle's law, after we had corrected for the thermal properties and impedance of the plethysmograph (17). We then measured respiratory system impedance (Z rs) using a wavetube system adapted for use in small animals (39,47) and a modification of the forced oscillation technique (47) as previously described (24). The constant phase model was fit to Z rs to generate the parameters of airway resistance (Raw), tissue damping (G), and tissue elastance (H).…”

Section: Particulatesmentioning

confidence: 99%

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The effects of electronic cigarette aerosol exposure on inflammation and lung function in mice

Larcombe

Janka

Mullins

et al. 2017

American Journal of Physiology-Lung Cellular and Molecular Phys

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115

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Electronic cigarette usage is increasing worldwide, yet there is a paucity of information on the respiratory health effects of electronic cigarette aerosol exposure. This study aimed to assess whether exposure to electronic cigarette (e-cigarette) aerosol would alter lung function and pulmonary inflammation in mice and to compare the severity of any alterations with mice exposed to mainstream tobacco smoke. Female BALB/c mice were exposed for 8 wk to tobacco smoke, medical air (control), or one of four different types of e-cigarette aerosol. E-cigarette aerosols varied depending on nicotine content (0 or 12 mg/ml) and the main excipient (propylene glycol or glycerin). Twenty-four hours after the final exposure, we measured pulmonary inflammation, lung volume, lung mechanics, and responsiveness to methacholine. Mice exposed to tobacco cigarette smoke had increased pulmonary inflammation and responsiveness to methacholine compared with air controls. Mice exposed to e-cigarette aerosol did not have increased inflammation but did display decrements in parenchymal lung function at both functional residual capacity and high transrespiratory pressures. Mice exposed to glycerin-based e-cigarette aerosols were also hyperresponsive to methacholine regardless of the presence or absence of nicotine. This study shows, for the first time, that exposure to e-cigarette aerosol during adolescence and early adulthood is not harmless to the lungs and can result in significant impairments in lung function.

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“…Animal preparation (postexposure). Twenty-four hours after the last exposure, mice were prepared for lung function assessment as previously described (24).…”

Section: Methodsmentioning

confidence: 99%

Section: Particulatesmentioning

confidence: 99%

The effects of electronic cigarette aerosol exposure on inflammation and lung function in mice

Larcombe

Janka

Mullins

et al. 2017

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

115

View full text Add to dashboard Cite

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“…Although alteration of the lung’s cholinergic system has not previously been demonstrated in advanced pulmonary TB, pathological manifestations similar to those occurring in COPD are characteristically observed ( 33 ). Larcombe and colleagues previously demonstrated that basal cholinergic tone is completely absent in BALB/c mice ( 34 ). However, using a well-characterized BALB/c mouse TB model ( 20 ), we have shown for the first time that upregulation of the lung’s non-neuronal cholinergic system occurs during experimental pulmonary TB.…”

Section: Discussionmentioning

confidence: 99%

The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis

et al. 2021

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The cholinergic system is present in both bacteria and mammals and regulates inflammation during bacterial respiratory infections through neuronal and non-neuronal production of acetylcholine (ACh) and its receptors. However, the presence of this system during the immunopathogenesis of pulmonary tuberculosis (TB) in vivo and in its causative agent Mycobacterium tuberculosis (Mtb) has not been studied. Therefore, we used an experimental model of progressive pulmonary TB in BALB/c mice to quantify pulmonary ACh using high-performance liquid chromatography during the course of the disease. In addition, we performed immunohistochemistry in lung tissue to determine the cellular expression of cholinergic system components, and then administered nicotinic receptor (nAChR) antagonists to validate their effect on lung bacterial burden, inflammation, and pro-inflammatory cytokines. Finally, we subjected Mtb cultures to colorimetric analysis to reveal the production of ACh and the effect of ACh and nAChR antagonists on Mtb growth. Our results show high concentrations of ACh and expression of its synthesizing enzyme choline acetyltransferase (ChAT) during early infection in lung epithelial cells and macrophages. During late progressive TB, lung ACh upregulation was even higher and coincided with ChAT and α7 nAChR subunit expression in immune cells. Moreover, the administration of nAChR antagonists increased pro-inflammatory cytokines, reduced bacillary loads and synergized with antibiotic therapy in multidrug resistant TB. Finally, in vitro studies revealed that the bacteria is capable of producing nanomolar concentrations of ACh in liquid culture. In addition, the administration of ACh and nicotinic antagonists to Mtb cultures induced or inhibited bacterial proliferation, respectively. These results suggest that Mtb possesses a cholinergic system and upregulates the lung non-neuronal cholinergic system, particularly during late progressive TB. The upregulation of the cholinergic system during infection could aid both bacterial growth and immunomodulation within the lung to favor disease progression. Furthermore, the therapeutic efficacy of modulating this system suggests that it could be a target for treating the disease.

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“…However, there are a few studies that apply the infusion technique. [63][64][65][66] The continuous infusion protocol selected in these studies may pertain to the mechanical ventilator/ technique used (wavetube) and time length of the applied volume perturbation, which is up to 16 s each. The assessment of respiratory mechanics is generally conducted using the mean of three perturbations in the wavetube technique.…”

Section: Mch Infusionmentioning

confidence: 99%

Drug class effects on respiratory mechanics in animal models: access and applications

Oliveira

Lino-Alvarado

Moriya

et al. 2021

Exp Biol Med (Maywood)

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Assessment of respiratory mechanics extends from basic research and animal modeling to clinical applications in humans. However, to employ the applications in human models, it is desirable and sometimes mandatory to study non-human animals first. To acquire further precise and controlled signals and parameters, the animals studied must be further distant from their spontaneous ventilation. The majority of respiratory mechanics studies use positive pressure ventilation to model the respiratory system. In this scenario, a few drug categories become relevant: anesthetics, muscle blockers, bronchoconstrictors, and bronchodilators. Hence, the main objective of this study is to briefly review and discuss each drug category, and the impact of a drug on the assessment of respiratory mechanics. Before and during the positive pressure ventilation, the experimental animal must be appropriately sedated and anesthetized. The sedation will lower the pain and distress of the studied animal and the plane of anesthesia will prevent the pain. With those drugs, a more controlled procedure is carried out; further, because many anesthetics depress the respiratory system activity, a minimum interference of the animal’s respiration efforts are achieved. The latter phenomenon is related to muscle blockers, which aim to minimize respiratory artifacts that may interfere with forced oscillation techniques. Generally, the respiratory mechanics are studied under appropriate anesthesia and muscle blockage. The application of bronchoconstrictors is prevalent in respiratory mechanics studies. To verify the differences among studied groups, it is often necessary to challenge the respiratory system, for example, by pharmacologically inducing bronchoconstriction. However, the selected bronchoconstrictor, doses, and administration can affect the evaluation of respiratory mechanics. Although not prevalent, studies have applied bronchodilators to return (airway resistance) to the basal state after bronchoconstriction. The drug categories can influence the mathematical modeling of the respiratory system, systemic conditions, and respiratory mechanics outcomes.

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Absence of cholinergic airway tone in normal BALB/c mice

Cited by 10 publications

References 41 publications

The effects of electronic cigarette aerosol exposure on inflammation and lung function in mice

The effects of electronic cigarette aerosol exposure on inflammation and lung function in mice

The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis

Drug class effects on respiratory mechanics in animal models: access and applications

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