scholarly journals Reduced mucociliary clearance in old mice is associated with a decrease in Muc5b mucin

2016 ◽  
Vol 310 (9) ◽  
pp. L860-L867 ◽  
Author(s):  
Barbara R. Grubb ◽  
Alessandra Livraghi-Butrico ◽  
Troy D. Rogers ◽  
Weining Yin ◽  
Brian Button ◽  
...  
Keyword(s):  
Mucociliary Clearance ◽  
Respiratory Infections ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
The Elderly ◽  
Older Individuals ◽  
Wild Type ◽  
Tracheal Tissue ◽  
Bronchial Tissue ◽  
Old Mice

Respiratory infections are a major cause of morbidity and mortality in the elderly. Previous reports have suggested that mucociliary clearance (MCC) is impaired in older individuals, but the cause is unclear. To unravel the mechanisms responsible for the age-associated decline in MCC, we investigated the MCC system in young (3 mo) and old (2 yr) C57BL/6 mice. We found that old mice had significantly reduced MCC function in both the upper and lower airways compared with young mice. Measurement of bioelectric properties of isolated tracheal and bronchial tissue revealed a significant decrease in Cl− secretion, suggesting that the older mice may have a reduced ability to maintain a sufficiently hydrated airway surface for efficient MCC. Ciliary beat frequency was also observed to be reduced in the older animals; however, this reduction was small relative to the reduction in MCC. Interestingly, the level of the major secreted mucin, Muc5b, was found to be reduced in both bronchioalveolar lavage and isolated tracheal tissue. Our previous studies of Muc5b−/− mice have demonstrated that Muc5b is essential for normal MCC in the mouse. Furthermore, examination of Muc5b+/− and wild-type animals revealed that heterozygous animals, which secrete ∼50% of the wild-type level of Muc5b, also demonstrate a markedly reduced level of MCC, confirming the importance of Muc5b levels to MCC. These results demonstrate that aged mice exhibit a decrease in MCC and suggest that a reduced level of secretion of both Cl− and Muc5b may be responsible.

scholarly journals Differential effect of anesthetics on mucociliary clearance in vivo in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyle S. Feldman ◽  
Eunwon Kim ◽  
Michael J. Czachowski ◽  
Yijen Wu ◽  
Cecilia W. Lo ◽  
...  
Keyword(s):  
Mucociliary Clearance ◽  
Defense Mechanism ◽  
Ex Vivo ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Wild Type ◽  
Sulfur Colloid ◽  
Ct System

AbstractRespiratory mucociliary clearance (MCC) is a key defense mechanism that functions to entrap and transport inhaled pollutants, particulates, and pathogens away from the lungs. Previous work has identified a number of anesthetics to have cilia depressive effects in vitro. Wild-type C57BL/6 J mice received intra-tracheal installation of 99mTc-Sulfur colloid, and were imaged using a dual-modality SPECT/CT system at 0 and 6 h to measure baseline MCC (n = 8). Mice were challenged for one hour with inhalational 1.5% isoflurane, or intraperitoneal ketamine (100 mg/kg)/xylazine (20 mg/kg), ketamine (0.5 mg/kg)/dexmedetomidine (50 mg/kg), fentanyl (0.2 mg/kg)/1.5% isoflurane, propofol (120 mg/Kg), or fentanyl/midazolam/dexmedetomidine (0.025 mg/kg/2.5 mg/kg/0.25 mg/kg) prior to MCC assessment. The baseline MCC was 6.4%, and was significantly reduced to 3.7% (p = 0.04) and 3.0% (p = 0.01) by ketamine/xylazine and ketamine/dexmedetomidine challenge respectively. Importantly, combinations of drugs containing fentanyl, and propofol in isolation did not significantly depress MCC. Although no change in cilia length or percent ciliation was expected, we tried to correlate ex-vivo tracheal cilia ciliary beat frequency and cilia-generated flow velocities with MCC and found no correlation. Our results indicate that anesthetics containing ketamine (ketamine/xylazine and ketamine/dexmedetomidine) significantly depress MCC, while combinations containing fentanyl (fentanyl/isoflurane, fentanyl/midazolam/dexmedetomidine) and propofol do not. Our method for assessing MCC is reproducible and has utility for studying the effects of other drug combinations.

scholarly journals Aging causes a slowing in ciliary beat frequency, mediated by PKCε

2014 ◽  
Vol 306 (6) ◽  
pp. L584-L589 ◽  
Author(s):  
K. L. Bailey ◽  
S. J. Bonasera ◽  
M. Wilderdyke ◽  
B. W. Hanisch ◽  
J. A. Pavlik ◽  
...  
Keyword(s):  
Octanoic Acid ◽  
Mucociliary Clearance ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
The Elderly ◽  
First Line ◽  
Kinase C ◽  
Threefold Increase ◽  
Similar Decrease ◽  
Ciliary Beat

The elderly are at much higher risk for developing pneumonia than younger individuals. Pneumonia is a leading cause of death and is the third most common reason for hospitalization in the elderly. One reason that elderly people may be more susceptible to pneumonia is a breakdown in the lung's first line of defense, mucociliary clearance. Cilia beat in a coordinated manner to propel out invading microorganisms and particles. Ciliary beat frequency (CBF) is known to slow with aging, however, little is known about the mechanism(s) involved. We compared the CBF in BALB/c and C57BL/6 mice aged 2, 12, and 24 mo and found that CBF diminishes with age. Cilia in the mice at age 12 and 24 mo retained their ability to be stimulated by the β2 agonist procaterol. To help determine the mechanism of ciliary slowing, we measured protein kinase C alpha and epsilon (PKCα and PKCε) activity. There were no activity differences in PKCα between the mice aged 2, 12, or 24 mo. However, we demonstrated a significantly higher PKCε activity in the mice at 12 and 24 mo than the in the mice 2 mo of age. The increase in activity is likely due to a nearly threefold increase in PKCε protein in the lung during aging. To strengthen the connection between activation of PKCε and ciliary slowing, we treated tracheas of mice at 2 mo with the PKCε agonist 8-[2-(2-pentylcyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA). We noted a similar decrease in baseline CBF, and the cilia remained sensitive to stimulation with β2 agonists. The mechanisms for the slowing of baseline CBF have not been previously determined. In this mouse model of aging we were able to show that decreases in CBF are related to an increase in PKCε activity.

scholarly journals Interaction between ion transporters and the mucociliary transport system in dog and baboon

1997 ◽  
Vol 83 (4) ◽  
pp. 1348-1359 ◽  
Author(s):  
Scot L. Winters ◽  
Donovan B. Yeates
Keyword(s):  
Respiratory Tract ◽  
Transport System ◽  
Mucociliary Clearance ◽  
Beat Frequency ◽  
Nuclear Imaging ◽  
Ciliary Beat Frequency ◽  
Lung Deposition ◽  
Mucociliary Transport ◽  
Ion Transporters ◽  
Dry Air

Winters, Scot L., and Donovan B. Yeates. Interaction between ion transporters and the mucociliary transport system in dog and baboon. J. Appl. Physiol. 83(4): 1348–1359, 1997.—To gain insight into the role of epithelial ion channels, pumps, and cotransporters in regulating airway water and mucociliary transport, we administered inhibitors of the Na+ channel (amiloride), 3Na-2K-adenosinetriphosphatase (acetylstrophanthidin), and Na-K-2Cl cotransporter (furosemide) to anesthetized dogs and/or baboons. Tracheal ciliary beat frequency was measured by using heterodyne laser light scattering. Tracheal mucus velocity (TMV) and bronchial mucociliary clearance (BMC) or lung mucociliary clearance were measured by using radioaerosols and nuclear imaging. Respiratory tract fluid output was collected by using a secretion-collecting endotracheal tube. In six dogs, amiloride aerosol [lung deposition, 96 ± 11 μg (means ± SE)] had minimal effect, whereas acetylstrophanthidin aerosol (lung deposition, 71 ± 9 μg) increased BMC, and furosemide (40 mg iv) markedly increased TMV. In five baboons, TMV increased after iv furosemide administration (2 mg/kg) as well as by aerosol (lung deposition, 20 ± 3 mg), coincident with increases in ciliary-mucus coupling from 11.5 ± 0.1 to 29.5 ± 0.4 and 46.5 ± 0.7 μm/beat, respectively. Furosemide also increased lung mucociliary clearance in baboons. In dogs, respiratory tract fluid output increased after intravenous furosemide from 2.2 ± 0.5 to 6.8 ± 1.7 mg/min. When combined with dry-air inhalation, furosemide failed to stimulate TMV and reversed the inhibition of BMC by dry air. Thus pharmacological manipulation of the Na-K-2Cl cotransporter and the 3Na-2K-adenosinetriphosphatase pump may provide increases of clinical relevance in airway hydration and mucociliary transport.

scholarly journals Cinnamaldehyde in flavored e-cigarette liquids temporarily suppresses bronchial epithelial cell ciliary motility by dysregulation of mitochondrial function

2019 ◽  
Vol 316 (3) ◽  
pp. L470-L486 ◽  
Author(s):  
Phillip W. Clapp ◽  
Katelyn S. Lavrich ◽  
Catharina A. van Heusden ◽  
Eduardo R. Lazarowski ◽  
Johnny L. Carson ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Respiratory Infections ◽  
Adenine Nucleotide ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Bronchial Epithelial Cell ◽  
Dependent Manner ◽  
Bronchial Epithelial ◽  
Ciliary Motility ◽  
Atp Levels

Aldehydes in cigarette smoke (CS) impair mitochondrial function and reduce ciliary beat frequency (CBF), leading to diminished mucociliary clearance (MCC). However, the effects of aldehyde e-cigarette flavorings on CBF are unknown. The purpose of this study was to investigate whether cinnamaldehyde, a flavoring agent commonly used in e-cigarettes, disrupts mitochondrial function and impairs CBF on well-differentiated human bronchial epithelial (hBE) cells. To this end, hBE cells were exposed to diluted cinnamon-flavored e-liquids and vaped aerosol and assessed for changes in CBF. hBE cells were subsequently exposed to various concentrations of cinnamaldehyde to establish a dose-response relationship for effects on CBF. Changes in mitochondrial oxidative phosphorylation and glycolysis were evaluated by Seahorse Extracellular Flux Analyzer, and adenine nucleotide levels were quantified by HPLC. Both cinnamaldehyde-containing e-liquid and vaped aerosol rapidly yet transiently suppressed CBF, and exposure to cinnamaldehyde alone recapitulated this effect. Cinnamaldehyde impaired mitochondrial respiration and glycolysis in a dose-dependent manner, and intracellular ATP levels were significantly but temporarily reduced following exposure. Addition of nicotine had no effect on the cinnamaldehyde-induced suppression of CBF or mitochondrial function. These data indicate that cinnamaldehyde rapidly disrupts mitochondrial function, inhibits bioenergetic processes, and reduces ATP levels, which correlates with impaired CBF. Because normal ciliary motility and MCC are essential respiratory defenses, inhalation of cinnamaldehyde may increase the risk of respiratory infections in e-cigarette users.

Effect of Myrtol Standardized and Other Substances on the Respiratory Tract: Ciliary Beat Frequency and Mucociliary Clearance as Parameters

2012 ◽  
Vol 29 (4) ◽  
pp. 350-358 ◽  
Author(s):  
Frank Begrow ◽  
Corinna Böckenholt ◽  
Martina Ehmen ◽  
Thomas Wittig ◽  
Eugen J. Verspohl
Keyword(s):  
Respiratory Tract ◽  
Mucociliary Clearance ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Other Substances ◽  
Ciliary Beat

scholarly journals Streptococcus pneumoniae-Induced Inhibition of Rat Ependymal Cilia Is Attenuated by Antipneumolysin Antibody

2004 ◽  
Vol 72 (11) ◽  
pp. 6694-6698 ◽  
Author(s):  
Robert A. Hirst ◽  
Bashir J. Mohammed ◽  
Timothy J. Mitchell ◽  
Peter W. Andrew ◽  
Christopher O'Callaghan
Keyword(s):  
Streptococcus Pneumoniae ◽  
Therapeutic Potential ◽  
Ependymal Cell ◽  
Ex Vivo ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Ependymal Cells ◽  
Wild Type ◽  
Ependymal Cilia ◽  
The Brain

ABSTRACT Ciliated ependymal cells line the ventricular surfaces and aqueducts of the brain. In ex vivo experiments, pneumolysin caused rapid inhibition of the ependymal ciliary beat frequency and caused ependymal cell disruption. Wild-type pneumococci and pneumococci deficient in pneumolysin caused ciliary slowing, but penicillin lysis of wild-type, not pneumolysin-deficient, pneumococci increased the extent of ciliary inhibition. This effect was abolished by antipneumolysin antibody. Ependymal ciliary stasis by purified pneumolysin was also blocked by the addition of antipneumolysin monoclonal antibodies. These data show that antibiotic lysis of Streptococcus pneumoniae can be detrimental to the ciliated ependyma and that antipneumolysin antibody may have a therapeutic potential.

scholarly journals Effect of betamethasone and betamethasone with neomycin nasal drops on human nasal mucociliary clearance and ciliary beat frequency.

Thorax ◽  
1985 ◽  
Vol 40 (8) ◽  
pp. 607-612 ◽  
Author(s):  
P J Stanley ◽  
W M Griffin ◽  
R Wilson ◽  
M A Greenstone ◽  
I S Mackay ◽  
...  
Keyword(s):  
Mucociliary Clearance ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Nasal Mucociliary Clearance ◽  
Ciliary Beat
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