Differential in Vivo Effects of Whole Cigarette Smoke Exposure Versus Cigarette Smoke Extract on Mouse Ciliated Tracheal Epithelium

Elliott, Margaret K.; Sisson, Joseph H.; West, William W.; Wyatt, Todd A.

doi:10.1080/01902140600710546

Cited by 45 publications

(46 citation statements)

References 55 publications

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“…Interestingly, when chronically exposed to ethanol, the effect was quite opposite and ciliary beating was decreased (Wyatt and Sisson, 2001). This chronic desensitization of cilia stimulation by ethanol has also been demonstrated in vivo in rat (Wyatt et al, 2004) and mouse (Elliott et al, 2006) models. Unique to our current study is the observation that maternal transmission of ethanol-mediated desensitization occurs in the full-term lamb as well.…”

Section: Discussionsupporting

confidence: 55%

Maternal alcohol ingestion reduces surfactant protein A expression by preterm fetal lung epithelia

Lazic¹,

Wyatt²,

Matić³

et al. 2007

Alcohol

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In addition to neurodevelopmental effects, alcohol consumption at high levels during pregnancy is associated with immunomodulation and premature birth. Premature birth, in turn, is associated with increased susceptibility to various infectious agents such as Respiratory Syncytial Virus (RSV). The initial line of pulmonary innate defense includes the mucociliary apparatus, which expels microorganisms trapped within the airway secretions. Surfactant proteins A and D (SP-A and SP-D, respectively) are additional components of pulmonary innate immunity and have an important role in pulmonary defense against inhaled pathogens. The purpose of this study was to determine if chronic alcohol consumption during the third trimester of pregnancy alters the function of the mucociliary apparatus and expression of SP-A and SP-D of fetal lung epithelia. Sixteen, date-mated ewes were assigned to two different groups; an ethanol exposed group in which ewes received ethanol through surgically implanted intra-abomasal cannula during the third trimester of pregnancy, and a control group in which ewes received the equivalent amount of water instead of ethanol. Within these two groups, ewes were further randomly assigned to a full-term group in which the lambs were naturally delivered, and a pre-term group in which the lambs were delivered prematurely via an abdominal incision and uterotomy. Ethanol was administered 5 times a week as a 40% solution at 1gr/kg of body weight. The mean maternal serum alcohol concentration (SAC) measured 6 hr post administration was 16.3 +/− 4.36 mg/dL. Tracheas from 6 full-term lambs were collected to assess ciliary beat frequency (CBF). The lung tissue from all (24) lambs was collected for immunohistochemistry (IHC) analysis of SP-A and SP-D protein production and fluorogenic realtime quantitative polymerase chain reaction analysis (qPCR) of SP-A and SP-D mRNA levels. Exposure to ethanol during pregnancy significantly blocked stimulated increase in CBF though ethanol-mediated desensitization of cAMP-dependant protein kinase (PKA). In addition, pre-term born/ethanol-exposed lambs showed significantly decreased SP-A m-RNA expression when compared to the pre-term born/control group (p=0.004); no significant changes were seen with SP-D. The full-term/ethanol exposed lambs had no significant alterations in mRNA levels, but had significantly less detectable SP-A protein when compared to the full-term/control lambs (p=0.02).Corresponding author: Tatjana Lazic, DVM, MS, 2740 Veterinary Medicine, Department of Veterinary Pathology, Iowa State University, Ames, Iowa 50011-1250, 515-294-6688, FAX 515-294-5423, tlazic@iastate.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process error...

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Section: Discussionsupporting

confidence: 55%

Maternal alcohol ingestion reduces surfactant protein A expression by preterm fetal lung epithelia

Lazic¹,

Wyatt²,

Matić³

et al. 2007

Alcohol

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“…In vivo studies with ciliated epithelium similarly demonstrate a transient, but significant increase in baseline CBF in mice exposed to CS and cigarette smoke extract (CSE). (7,8) An initial and rapid increase in MCC was also observed in rats exposed to unfiltered CS. (9) Other studies, however, show significant decreases in CBF with exposure to CS.…”

Section: Introductionmentioning

confidence: 77%

“…Because in vitro studies have been inconclusive on whether CSE exposure results in CBF stimulation or inhibition (7)(8)(9)11,21) we assayed CBF in a cell-free preparation of ciliary axonemes exposed to CSE. Given the high incidence of pulmonary disease in tobacco users, we hypothesized that CSE would alter CBF in a cell-free axoneme model.…”

Section: Introductionmentioning

confidence: 99%

Particulate Matter in Cigarette Smoke Increases Ciliary Axoneme Beating Through Mechanical Stimulation

Navarrette¹,

Sisson²,

Nance

et al. 2012

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: The lung's ability to trap and clear foreign particles via the mucociliary elevator is an important mechanism for protecting the lung against respirable irritants and microorganisms. Although cigarette smoke (CS) exposure and particulate inhalation are known to alter mucociliary clearance, little is known about how CS and nanoparticles (NPs) modify cilia beating at the cytoskeletal infrastructure, or axonemal, level. Methods: We used a cell-free model to introduce cigarette smoke extract (CSE) and NPs with variant size and surface chemistry to isolated axonemes and measured changes in ciliary motility. We hypothesized that CSE would alter cilia beating and that alterations in ciliary beat frequency (CBF) due to particulate matter would be size-and surface chemistry-dependent. Demembranated axonemes were isolated from ciliated bovine tracheas and exposed to adenosine triphosphate (ATP) to initiate motility. CBF was measured in response to 5% CSE, CSE filtrate, and carboxyl-modified (COOH), sulphate (SO 4 )-modified (sulfonated), or PEG-coated polystyrene (PS) latex NPs ranging in size from 40 nm to 500 nm. Results: CSE concentrations as low as 5% resulted in rapid, significant stimulation of CBF ( p < 0.05 vs. baseline control). Filtering CSE through a 0.2-lm filter attenuated this effect. Introduction of sulphate-modified PS beads *300 nm in diameter resulted in a similar increase in CBF above baseline ATP levels. Uncharged, PEG-coated beads had no effect on CBF regardless of size. Similarly, COOH-coated particles less than 200 nm in diameter did not alter ciliary motility. However, COOH-coated PS particles larger than 300 nm increased CBF significantly and increased the number of motile points. Conclusions: These data show that NPs, including those found in CSE, mechanically stimulate axonemes in a size-and surface chemistry-dependent manner. Alterations in ciliary motility due to physicochemical properties of NPs may be important for inhalational lung injury and efficient drug delivery of respirable particles.

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“…Lungs from AKO and wildtype mice were fixed with 10% neutral buffered formalin (pH 7.2) as previously described by Elliot et al (15). Following fixation, lungs were paraffin embedded, serial sectioned (4 -5 m), and stained with hematoxylin and eosin, revealing normal appearing cilia and pseudocolumnar epithelium in all four AKO and wild-type mouse tracheal rings (MTRs) (Fig.…”

Section: Methodsmentioning

confidence: 99%

Adenosine activation of A_2Breceptor(s) is essential for stimulated epithelial ciliary motility and clearance

Allen‐Gipson¹,

Blackburn

Schneider

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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sine activation of A2B receptor(s) is essential for stimulated epithelial ciliary motility and clearance. Am J Physiol Lung Cell Mol Physiol 301: L171-L180, 2011. First published May 27, 2011 doi:10.1152/ajplung.00203.2010.-Mucociliary clearance, vital to lung clearance, is dependent on cilia beat frequency (CBF), coordination of cilia, and the maintenance of periciliary fluid. Adenosine, the metabolic breakdown product of ATP, is an important modulator of ciliary motility. However, the contributions of specific adenosine receptors to key airway ciliary motility processes are unclear. We hypothesized that adenosine modulates ciliary motility via activation of its cell surface receptors (A1, A2A, A2B, or A3). To test this hypothesis, mouse tracheal rings (MTRs) excised from wild-type and adenosine receptor knockout mice (A1, A2A, A2B, or A3, respectively), and bovine ciliated bronchial epithelial cells (BBECs) were stimulated with known cilia activators, isoproterenol (ISO; 10 M) and/or procaterol (10 M), in the presence or absence of 5=-(Nethylcarboxamido) adenosine (NECA), a nonselective adenosine receptor agonist [100 nM (A1, A2A, A3); 10 M (A2B)], and CBF was measured. Cells and MTRs were also stimulated with NECA (100 nM or 10 M) in the presence and absence of adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (10 M). Both ISO and procaterol stimulated CBF in untreated cells and/or MTRs from both wild-type and adenosine knockout mice by ϳ3 Hz. Likewise, CBF significantly increased ϳ2-3 Hz in BBECs and wild-type MTRs stimulated with NECA. MTRs from A1, A2A, and A3 knockout mice stimulated with NECA also demonstrated an increase in CBF. However, NECA failed to stimulate CBF in MTRs from A2B knockout mice. To confirm the mechanism by which adenosine modulates CBF, protein kinase activity assays were conducted. The data revealed that NECA-stimulated CBF is mediated by the activation of cAMP-dependent PKA. Collectively, these data indicate that purinergic stimulation of CBF requires A2B adenosine receptor activation, likely via a PKA-dependent pathway. mucociliary clearance; knockout mouse model; bovine bronchial epithelial cells MUCOCILIARY TRANSPORT is an important host defense mechanism in the lung by which the coordinated beating of cilia continuously clears the lung of aspirated microorganisms and inhaled debris. This transport is dependent on the ciliary motion of airway epithelium, physicochemical properties of periciliary fluid, and mucus secretion (45, 50). Regulation of airway ciliary motility is critical because mucociliary transport is considered the first line of defense between the lung and the environment. Stressful conditions such as exercise or inflammation cause cilia in the airway to beat faster, increase clearance, and move an increased number of inhaled particles (2). As a consequence, mucociliary transport is a regulable host defense that can be activated under numerous conditions. It has been well described that ATP, a signaling molecule released by the airw...

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Differential in Vivo Effects of Whole Cigarette Smoke Exposure Versus Cigarette Smoke Extract on Mouse Ciliated Tracheal Epithelium

Cited by 45 publications

References 55 publications

Maternal alcohol ingestion reduces surfactant protein A expression by preterm fetal lung epithelia

Maternal alcohol ingestion reduces surfactant protein A expression by preterm fetal lung epithelia

Particulate Matter in Cigarette Smoke Increases Ciliary Axoneme Beating Through Mechanical Stimulation

Adenosine activation of A_2Breceptor(s) is essential for stimulated epithelial ciliary motility and clearance

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Differential in Vivo Effects of Whole Cigarette Smoke Exposure Versus Cigarette Smoke Extract on Mouse Ciliated Tracheal Epithelium

Cited by 45 publications

References 55 publications

Maternal alcohol ingestion reduces surfactant protein A expression by preterm fetal lung epithelia

Maternal alcohol ingestion reduces surfactant protein A expression by preterm fetal lung epithelia

Particulate Matter in Cigarette Smoke Increases Ciliary Axoneme Beating Through Mechanical Stimulation

Adenosine activation of A2Breceptor(s) is essential for stimulated epithelial ciliary motility and clearance

Contact Info

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Adenosine activation of A_2Breceptor(s) is essential for stimulated epithelial ciliary motility and clearance