LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 8 of total 8

Search options

  1. Article ; Online: CFTR-rich ionocytes mediate chloride absorption across airway epithelia

    Lei Lei / Soumba Traore / Guillermo S. Romano Ibarra / Philip H. Karp / Tayyab Rehman / David K. Meyerholz / Joseph Zabner / David A. Stoltz / Patrick L. Sinn / Michael J. Welsh / Paul B. McCray Jr. / Ian M. Thornell

    The Journal of Clinical Investigation, Vol 133, Iss

    2023  Volume 20

    Abstract: The volume and composition of a thin layer of liquid covering the airway surface defend the lung from inhaled pathogens and debris. Airway epithelia secrete Cl– into the airway surface liquid through cystic fibrosis transmembrane conductance regulator ( ... ...

    Abstract The volume and composition of a thin layer of liquid covering the airway surface defend the lung from inhaled pathogens and debris. Airway epithelia secrete Cl– into the airway surface liquid through cystic fibrosis transmembrane conductance regulator (CFTR) channels, thereby increasing the volume of airway surface liquid. The discovery that pulmonary ionocytes contain high levels of CFTR led us to predict that ionocytes drive secretion. However, we found the opposite. Elevating ionocyte abundance increased liquid absorption, whereas reducing ionocyte abundance increased secretion. In contrast to other airway epithelial cells, ionocytes contained barttin/Cl– channels in their basolateral membrane. Disrupting barttin/Cl– channel function impaired liquid absorption, and overexpressing barttin/Cl– channels increased absorption. Together, apical CFTR and basolateral barttin/Cl– channels provide an electrically conductive pathway for Cl– flow through ionocytes, and the transepithelial voltage generated by apical Na+ channels drives absorption. These findings indicate that ionocytes mediate liquid absorption, and secretory cells mediate liquid secretion. Segregating these counteracting activities to distinct cell types enables epithelia to precisely control the airway surface. Moreover, the divergent role of CFTR in ionocytes and secretory cells suggests that cystic fibrosis disrupts both liquid secretion and absorption.
    Keywords Cell biology ; Pulmonology ; Medicine ; R
    Subject code 621
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: Transduction of Pig Small Airway Epithelial Cells and Distal Lung Progenitor Cells by AAV4

    Oliver G. Chen / Steven E. Mather / Christian M. Brommel / Bradley A. Hamilton / Annie Ehler / Raul Villacreses / Reda E. Girgis / Mahmoud Abou Alaiwa / David A. Stoltz / Joseph Zabner / Xiaopeng Li

    Cells, Vol 10, Iss 1014, p

    2021  Volume 1014

    Abstract: Cystic fibrosis (CF) is caused by genetic mutations of the CF transmembrane conductance regulator (CFTR), leading to disrupted transport of Cl − and bicarbonate and CF lung disease featuring bacterial colonization and chronic infection in conducting ... ...

    Abstract Cystic fibrosis (CF) is caused by genetic mutations of the CF transmembrane conductance regulator (CFTR), leading to disrupted transport of Cl − and bicarbonate and CF lung disease featuring bacterial colonization and chronic infection in conducting airways. CF pigs engineered by mutating CFTR develop lung disease that mimics human CF, and are well-suited for investigating CF lung disease therapeutics. Clinical data suggest small airways play a key role in the early pathogenesis of CF lung disease, but few preclinical studies have focused on small airways. Efficient targeted delivery of CFTR cDNA to small airway epithelium may correct the CFTR defect and prevent lung infections. Adeno-associated virus 4 (AAV4) is a natural AAV serotype and a safe vector with lower immunogenicity than other gene therapy vectors such as adenovirus. Our analysis of AAV natural serotypes using cultured primary pig airway epithelia showed that AAV4 has high tropism for airway epithelia and higher transduction efficiency for small airways compared with large airways. AAV4 mediated the delivery of CFTR, and corrected Cl − transport in cultured primary small airway epithelia from CF pigs. Moreover, AAV4 was superior to all other natural AAV serotypes in transducing ITGα6β4 + pig distal lung progenitor cells. In addition, AAV4 encoding eGFP can infect pig distal lung epithelia in vivo. This study demonstrates AAV4 tropism in small airway progenitor cells, which it efficiently transduces. AAV4 offers a novel tool for mechanistical study of the role of small airway in CF lung pathogenesis in a preclinical large animal model.
    Keywords cystic fibrosis 1 ; CFTR ; small airway epithelia ; progenitor cells ; AAV4 ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Glycogen depletion can increase the specificity of mucin detection in airway tissues

    David K. Meyerholz / Amanda P. Beck / J. Adam Goeken / Mariah R. Leidinger / Georgina K. Ofori-Amanfo / Hannah C. Brown / Thomas R. Businga / David A. Stoltz / Leah R. Reznikov / Heather A. Flaherty

    BMC Research Notes, Vol 11, Iss 1, Pp 1-

    2018  Volume 5

    Abstract: Abstract Objective Mucin is an important parameter for detection and assessment in studies of airway disease including asthma and cystic fibrosis. Histochemical techniques are often used to evaluate mucin in tissues sections. Periodic acid Schiff (PAS) ... ...

    Abstract Abstract Objective Mucin is an important parameter for detection and assessment in studies of airway disease including asthma and cystic fibrosis. Histochemical techniques are often used to evaluate mucin in tissues sections. Periodic acid Schiff (PAS) is a common technique to detect neutral mucins in tissue, but this technique also detects other tissue components including cellular glycogen. We tested whether depletion of glycogen, a common cellular constituent, could impact the detection of mucin in the surface epithelium of the trachea. Results Normal tissues stained by PAS had significantly more staining than serial sections of glycogen-depleted tissue with PAS staining (i.e. dPAS technique) based on both quantitative analysis and semiquantitative scores. Most of the excess stain by the PAS technique was detected in ciliated cells adjacent to goblet cells. We also compared normal tissues using the Alcian blue technique, which does not have reported glycogen staining, with the dPAS technique. These groups had similar amounts of staining consistent with a high degree of mucin specificity. Our results suggest that when using PAS techniques to stain airways, the dPAS approach is preferred as it enhances the specificity for airway mucin.
    Keywords Mucus ; Mucin ; Periodic acid Schiff (PAS) ; Diastase-periodic acid Schiff (dPAS) ; Alcian blue ; Glycogen ; Medicine ; R ; Biology (General) ; QH301-705.5 ; Science (General) ; Q1-390
    Subject code 571
    Language English
    Publishing date 2018-10-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Acid-Sensing Ion Channel 1a Contributes to Airway Hyperreactivity in Mice.

    Leah R Reznikov / David K Meyerholz / Ryan J Adam / Mahmoud Abou Alaiwa / Omar Jaffer / Andrew S Michalski / Linda S Powers / Margaret P Price / David A Stoltz / Michael J Welsh

    PLoS ONE, Vol 11, Iss 11, p e

    2016  Volume 0166089

    Abstract: Neurons innervating the airways contribute to airway hyperreactivity (AHR), a hallmark feature of asthma. Several observations suggested that acid-sensing ion channels (ASICs), neuronal cation channels activated by protons, might contribute to AHR. For ... ...

    Abstract Neurons innervating the airways contribute to airway hyperreactivity (AHR), a hallmark feature of asthma. Several observations suggested that acid-sensing ion channels (ASICs), neuronal cation channels activated by protons, might contribute to AHR. For example, ASICs are found in vagal sensory neurons that innervate airways, and asthmatic airways can become acidic. Moreover, airway acidification activates ASIC currents and depolarizes neurons innervating airways. We found ASIC1a protein in vagal ganglia neurons, but not airway epithelium or smooth muscle. We induced AHR by sensitizing mice to ovalbumin and found that ASIC1a-/- mice failed to exhibit AHR despite a robust inflammatory response. Loss of ASIC1a also decreased bronchoalveolar lavage fluid levels of substance P, a sensory neuropeptide secreted from vagal sensory neurons that contributes to AHR. These findings suggest that ASIC1a is an important mediator of AHR and raise the possibility that inhibiting ASIC channels might be beneficial in asthma.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article ; Online: Lack of airway submucosal glands impairs respiratory host defenses

    Lynda S Ostedgaard / Margaret P Price / Kristin M Whitworth / Mahmoud H Abou Alaiwa / Anthony J Fischer / Akshaya Warrier / Melissa Samuel / Lee D Spate / Patrick D Allen / Brieanna M Hilkin / Guillermo S Romano Ibarra / Miguel E Ortiz Bezara / Brian J Goodell / Steven E Mather / Linda S Powers / Mallory R Stroik / Nicholas D Gansemer / Camilla E Hippee / Keyan Zarei /
    J Adam Goeken / Thomas R Businga / Eric A Hoffman / David K Meyerholz / Randall S Prather / David A Stoltz / Michael J Welsh

    eLife, Vol

    2020  Volume 9

    Abstract: Submucosal glands (SMGs) are a prominent structure that lines human cartilaginous airways. Although it has been assumed that SMGs contribute to respiratory defense, that hypothesis has gone without a direct test. Therefore, we studied pigs, which have ... ...

    Abstract Submucosal glands (SMGs) are a prominent structure that lines human cartilaginous airways. Although it has been assumed that SMGs contribute to respiratory defense, that hypothesis has gone without a direct test. Therefore, we studied pigs, which have lungs like humans, and disrupted the gene for ectodysplasin (EDA-KO), which initiates SMG development. EDA-KO pigs lacked SMGs throughout the airways. Their airway surface liquid had a reduced ability to kill bacteria, consistent with SMG production of antimicrobials. In wild-type pigs, SMGs secrete mucus that emerges onto the airway surface as strands. Lack of SMGs and mucus strands disrupted mucociliary transport in EDA-KO pigs. Consequently, EDA-KO pigs failed to eradicate a bacterial challenge in lung regions normally populated by SMGs. These in vivo and ex vivo results indicate that SMGs are required for normal antimicrobial activity and mucociliary transport, two key host defenses that protect the lung.
    Keywords sus scrofa ; host defense ; lung ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article: Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis

    Hoegger, Mark J / Alex J. Tucker / Andrew S. Michalski / Anthony J. Fischer / David A. Stoltz / Eric A. Hoffman / James D. McMenimen / Joseph Zabner / Lynda S. Ostedgaard / Maged A. Awadalla / Michael J. Welsh / Thomas O. Moninger

    Science. 2014 Aug. 15, v. 345, no. 6198

    2014  

    Abstract: A breathtaking tale of sticky mucus Patients with cystic fibrosis have difficulty breathing because their airways are clogged with thick mucus. Does this mucus accumulate because there is a defect in the way it is produced? Or does it accumulate because ... ...

    Abstract A breathtaking tale of sticky mucus Patients with cystic fibrosis have difficulty breathing because their airways are clogged with thick mucus. Does this mucus accumulate because there is a defect in the way it is produced? Or does it accumulate because of other disease features, such as dehydration or airway wall remodeling? Distinguishing between these possibilities is important for future drug development. In a study of piglets with cystic fibrosis, Hoegger et al. identify mucus production as the primary defect (see the Perspective by Wine). The airway glands of the piglets synthesized strands of mucus normally, but the strands were never released and stayed tethered to the gland ducts. Science , this issue p. 818; see also p. 730
    Keywords breathing ; cystic fibrosis ; drugs ; models ; mucus ; patients ; piglets ; wines
    Language English
    Dates of publication 2014-0815
    Size p. 818-822.
    Publishing place American Association for the Advancement of Science
    Document type Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.1255825
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Z 4' 46/137: Show issues
    + C 27: Show issues
    Z50.00 SC01: Show issues
    Z 8.9: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  7. Article ; Online: Expression of human paraoxonase 1 decreases superoxide levels and alters bacterial colonization in the gut of Drosophila melanogaster.

    Alejandro A Pezzulo / Emma E Hornick / Michael V Rector / Miriam Estin / Anna C Reisetter / Peter J Taft / Stephen C Butcher / A Brent Carter / J Robert Manak / David A Stoltz / Joseph Zabner

    PLoS ONE, Vol 7, Iss 8, p e

    2012  Volume 43777

    Abstract: Paraoxonases (PON) are a family of proteins (PON1, 2 and 3) with multiple enzymatic activities. PON1 interferes with homoserine lactone-mediated quorum sensing in bacteria and with reactive oxygen species (ROS) in humans and mice. PON1 gene mutations ... ...

    Abstract Paraoxonases (PON) are a family of proteins (PON1, 2 and 3) with multiple enzymatic activities. PON1 interferes with homoserine lactone-mediated quorum sensing in bacteria and with reactive oxygen species (ROS) in humans and mice. PON1 gene mutations have been linked to multiple traits, including aging, and diseases of the cardiovascular, nervous and gastrointestinal system. The overlapping enzymatic activities in the PON family members and high linkage disequilibrium rates within their polymorphisms confound animal and human studies of PON1 function. In contrast, arthropods such as Drosophila melanogaster have no PON homologs, resulting in an ideal model to study interactions between PON genotype and host phenotypes. We hypothesized that expression of PON1 in D. melanogaster would alter ROS. We found that PON1 alters expression of multiple oxidative stress genes and decreases superoxide anion levels in normal and germ-free D. melanogaster. We also found differences in the composition of the gut microbiota, with a remarkable increase in levels of Lactobacillus plantarum and associated changes in expression of antimicrobial and cuticle-related genes. PON1 expression directly decreased superoxide anion levels and altered bacterial colonization of the gut and its gene expression profile, highlighting the complex nature of the interaction between host genotype and gut microbiota. We speculate that the interaction between some genotypes and human diseases may be mediated by the presence of certain gut bacteria that can induce specific immune responses in the gut and other host tissues.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  8. Article ; Online: Glucose depletion in the airway surface liquid is essential for sterility of the airways.

    Alejandro A Pezzulo / Jeydith Gutiérrez / Kelly S Duschner / Kelly S McConnell / Peter J Taft / Sarah E Ernst / Timothy L Yahr / Kamal Rahmouni / Julia Klesney-Tait / David A Stoltz / Joseph Zabner

    PLoS ONE, Vol 6, Iss 1, p e

    2011  Volume 16166

    Abstract: Diabetes mellitus predisposes the host to bacterial infections. Moreover, hyperglycemia has been shown to be an independent risk factor for respiratory infections. The luminal surface of airway epithelia is covered by a thin layer of airway surface ... ...

    Abstract Diabetes mellitus predisposes the host to bacterial infections. Moreover, hyperglycemia has been shown to be an independent risk factor for respiratory infections. The luminal surface of airway epithelia is covered by a thin layer of airway surface liquid (ASL) and is normally sterile despite constant exposure to bacteria. The balance between bacterial growth and killing in the airway determines the outcome of exposure to inhaled or aspirated bacteria: infection or sterility. We hypothesized that restriction of carbon sources--including glucose--in the ASL is required for sterility of the lungs. We found that airway epithelia deplete glucose from the ASL via a novel mechanism involving polarized expression of GLUT-1 and GLUT-10, intracellular glucose phosphorylation, and low relative paracellular glucose permeability in well-differentiated cultures of human airway epithelia and in segments of airway epithelia excised from human tracheas. Moreover, we found that increased glucose concentration in the ASL augments growth of P. aeruginosa in vitro and in the lungs of hyperglycemic ob/ob and db/db mice in vivo. In contrast, hyperglycemia had no effect on intrapulmonary bacterial growth of a P. aeruginosa mutant that is unable to utilize glucose as a carbon source. Our data suggest that depletion of glucose in the airway epithelial surface is a novel mechanism for innate immunity. This mechanism is important for sterility of the airways and has implications in hyperglycemia and conditions that result in disruption of the epithelial barrier in the lung.
    Keywords Medicine ; R ; Science ; Q
    Subject code 670
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top