Variability of Airway Responses in Mice

Fernandez, Viana E.; McCaskill, V.; Atkins, Neal; Wanner, Adam

doi:10.1007/pl00007653

Cited by 10 publications

(10 citation statements)

References 14 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in remodeled mucus cell metaplastic airways, pretreatment of the airway directly with the MANS peptide before stimulation with the mucus secretagogue, methacholine, attenuated airway hyperresponsiveness in response to cumulative aerosol challenge with serotonin. Serotonin has been used previously in mice models to demonstrate responsiveness of the bronchial musculature and to accentuate differences in airway responsiveness between inbred mouse strains (7,12). To our knowledge, serotonin has not been shown to influence mucin secretion, and thus the MANS peptide-related attenuation of airway hyperresponsiveness would seemingly be associated with direct effects on airway smooth muscle contraction, indirect effects on baseline airway lumens related to inhibition of mucus secretion, or indirect effects of secreted mucins on airway reactivity.…”

Section: Discussionmentioning

confidence: 98%

“…On appropriate stimulation, the granules translocate to the apical borders of the cell, and, following fusion of granule membranes with the cellular plasma membrane, mucins are released onto airway epithelial surfaces via an exocytotic process (4,13). Nine mucins are currently recognized to be expressed in normal respiratory tract tissues (MUC1, 2, 4, 5AC, 5B, 7,8,13,and 19;Ref. 16).…”

mentioning

confidence: 99%

See 1 more Smart Citation

MARCKS-related peptide modulates in vivo the secretion of airway Muc5ac

Foster

Adler

Crews

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

In a mouse model of neutrophil elastase-induced bronchitis that exhibits goblet cell metaplasia and inflammation, we investigated the effects of intratracheal instillation of the MANS peptide, a peptide identical to the NH(2) terminus of the myristoylated alanine-rich C kinase substrate (MARCKS) on mucin protein airway secretion, inflammation, and airway reactivity. To induce mucus cell metaplasia in the airways, male BALB/c mice were treated repetitively with the serine protease, neutrophil elastase, on days 1, 4, and 7. On day 11, when goblet cell metaplasia was fully developed and profiles of proinflammatory cytokines were maximal, the animals were exposed to aerosolized methacholine after intratracheal instillation of MANS or a missense control peptide (RNS). MANS, but not RNS, attenuated the methacholine-stimulated secretion of the major respiratory mucin protein, Muc5ac (50% reduction). Concurrently, elastase-induced proinflammatory cytokines typically recovered in bronchoalveolar lavage (BAL), including KC, IL-1beta, IL-6, MCP-1, and TNFalpha, were reduced by the MANS peptide (mean levels decreased 50-60%). Secondary to the effects of MANS on mucin secretion and inflammation, mechanical lung function by forced oscillation technique was characterized with respect to airway reactivity in response to cumulative aerosol stimulation with serotonin. The MANS peptide was also found to effectively attenuate airway hyperresponsiveness to serotonin in this airway hypersecretory model. Collectively, these findings support the concept that even in airway epithelia remodeled with goblet cell metaplasia and in a state of mucin hypersecretion, exogenous attenuation of function of MARCKS protein via the MANS peptide decreases airway mucin secretion, inflammation, and hyperreactivity.

show abstract

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

MARCKS-related peptide modulates in vivo the secretion of airway Muc5ac

Foster

Adler

Crews

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…Alternatively, ultrasonic nebulization of bronchoconstrictor solutions (mg/ml) has been successfully applied in tracheostomized, ventilated mice (22). Such a direct cholinergic challenge to the airways is advantageous over systemic challenge not only because it better simulates physiological stimulation of airway smooth muscle in humans but also because systemic delivery of agonists has been reported to affect airways via reflex or humoral mechanisms (6,9).…”

Section: Discussionmentioning

confidence: 99%

Repetitive measurements of pulmonary mechanics to inhaled cholinergic challenge in spontaneously breathing mice

Glaab

Mitzner

Braun

et al. 2004

Journal of Applied Physiology

View full text Add to dashboard Cite

Repetitive measurements of pulmonary mechanics to inhaled cholinergic challenge in spontaneously breathing mice. J Appl Physiol 97: 1104 -1111, 2004. First published April 30, 2004 10.1152/japplphysiol.01182.2003.-Precise and repeatable measurements of pulmonary function in intact mice are becoming increasingly important for experimental investigations on various respiratory disorders including asthma. Here, we present validation of a novel in vivo method that, for the first time, combines direct and repetitive recordings of standard pulmonary mechanics with cholinergic aerosol challenges in anesthetized, orotracheally intubated, spontaneously breathing mice. We demonstrate that, in several groups of nonsensitized BALB/c mice, dose-related increases in pulmonary resistance and dynamic compliance to aerosolized methacholine are reproducible over short and extended intervals without causing detectable cytological alterations in the bronchoalveolar lavage or relevant histological changes in the proximal trachea and larynx regardless of the number of orotracheal intubations. Moreover, as further validation, we confirm that allergic mice, sensitized and challenged with Aspergillus fumigatus, were significantly more responsive to cholinergic challenge (P Ͻ 0.01) and exhibited marked eosinophilia and lymphocytosis in bronchoalveolar lavage fluids as well as significant pathological alterations in laryngotracheal histology compared with nonsensitized mice. We suggest that this approach will provide useful and necessary information on pulmonary mechanics in studies of various respiratory disorders in mice, including experimental models of asthma and chronic obstructive pulmonary disorder, investigations of pulmonary pharmacology, or more general investigations of the genetic determinants of lung function. experimental animal models; pulmonary function test; allergy; bronchial asthma THE ABILITY TO MEASURE PULMONARY FUNCTION in individual mice on repeated occasions is of great interest because of the prominent role played by these animals in genetic and translational research into the causes and mechanisms of respiratory and allergic diseases such as asthma (5,14). It is becoming increasingly evident that the real potential of gene-or cellbased applications in experimental asthma models is tightly linked to a solid understanding of the underlying respiratory pathophysiology (20). This growing interest in functional studies with mice that correlate in vitro findings with in vivo determination of respiratory physiology has prompted the search for measurements of pulmonary function that are valid and easy to implement.Existing methods for measuring respiratory function in mice in vivo include noninvasive and invasive technologies (2, 5). Noninvasive determination of airway responsiveness (AR) in intact conscious mice has gained much interdisciplinary interest as a convenient and effective method for screening respiratory function over extended periods of time (11).Concerns with existing noninvasive methods in spontaneously ...

show abstract

“…Fernandez et al (1999) generated a 3.1-m-diameter aerosol of serotonin or carbachol and delivered it through a cannula into the trachea of BALB/c and C57BL/6 mice. The significant differences in response, as compared to injection of these compounds, were attributed to unspecified differences between the mouse varieties.…”

Section: Discussionmentioning

confidence: 99%

“…It has also been observed that B6C3F 1 , C57B1/6, and DBA/2 mice demonstrate different induction levels of genotoxicity and hematotoxicity to chronic inhalation of benzene (Luke et al, 1988). More recently, Fernandez et al (1999) found differences in responses of two mouse strains (BALB/c and C57BL/6) to two common inhaled spasmogens: carbachol and serotonin. Strain-related differences in response are usually assumed to be related only to differences in metabolism or tissue sensitivity.…”

Section: Tion; Lung Castsmentioning

confidence: 98%

Dosimetry implications of upper tracheobronchial airway anatomy in two mouse varieties

Oldham

Phalen

2002

Anat. Rec.

View full text Add to dashboard Cite

Strain-and variety-related differences in responses of mice have been reported for a variety of inhaled particulate and gaseous materials. It is important to understand the potential contributions to such responses of differences in delivered doses to the respiratory tract as well as differences in biochemical processes. Deposition doses of inhaled particles are influenced by several factors, including airway anatomy, ventilation, and particle characteristics. Tracheobronchial airway morphometry for airway generations 1-6 of the BALB/c mouse was generated using replica lung casts prepared in situ. Measurements were performed on two groups: control and ovalbumin-sensitized male BALB/c mice. These measurements were compared with previously published airway morphometry of male B6C3F 1 mice. Sensitization did not significantly change measured airway dimensions in the BALB/c mouse. However, the two mouse varieties had significant differences in airway anatomy. The differences found in airway anatomy between mouse varieties correlated with differences in body length and chest circumference. Particle deposition predictions for both varieties of mice were performed for unit density spherical particles from 0.1 to 10 m in diameter at two ventilation rates using a published aerosol dosimetry computer code. Particle deposition in the proximal tracheobronchial tree ranged up to 3 times greater for the BALB/c mouse for a 2 m particle diameter and high ventilation rate. These differences in predicted particle deposition suggest that observed strain and variety differences in response to inhaled particulate matter may be in part due to differences in delivered doses to the respiratory tract. Anat Rec 268: 59 -65, 2002.

show abstract

Variability of Airway Responses in Mice

Cited by 10 publications

References 14 publications

MARCKS-related peptide modulates in vivo the secretion of airway Muc5ac

MARCKS-related peptide modulates in vivo the secretion of airway Muc5ac

Repetitive measurements of pulmonary mechanics to inhaled cholinergic challenge in spontaneously breathing mice

Dosimetry implications of upper tracheobronchial airway anatomy in two mouse varieties

Contact Info

Product

Resources

About