scholarly journals Early humoral defence: Contributing to confining COVID‐19 to conducting airways?

2021 ◽  
Author(s):  
Carl Persson
Keyword(s):  
Conducting Airways

New Ultrastructural Observations on Injury and Regeneration of Cilia in Mammalian Conducting Airway Epithelium

1981 ◽  
Vol 39 ◽  
pp. 624-625
Author(s):  
J.L. Carson ◽  
A.M. Collier
Keyword(s):  
Respiratory Tract ◽  
Airway Epithelium ◽  
Defense Mechanisms ◽  
Normal Growth ◽  
Fetal Lung ◽  
Secretory Cells ◽  
Airway Epithelial ◽  
Ciliated Cells ◽  
Conducting Airway ◽  
Conducting Airways

The ciliated cells lining the conducting airways of mammals are integral to the defense mechanisms of the respiratory tract, functioning in coordination with secretory cells in the removal of inhaled and cellular debris. The effects of various infectious and toxic agents on the structure and function of airway epithelial cell cilia have been studied in our laboratory, both of which have been shown to affect ciliary ultrastructure.These observations have led to questions about ciliary regeneration as well as the possible induction of ciliogenesis in response to cellular injury. Classical models of ciliogenesis in the conducting airway epithelium of the mammalian respiratory tract have been based primarily on observations of the developing fetal lung. These observations provide a plausible explanation for the embryological generation of ciliary beds lining the conducting airways but do little to account for subsequent differentiation of ciliated cells and ciliogenesis during normal growth and development.

Quantitative Microscopic Comparison of the Organization of the Lung in Transgenic Mice Expressing Transforming Growth Factor-α (TGF-α)

1996 ◽  
Vol 54 ◽  
pp. 14-15
Author(s):  
C. G. Plopper ◽  
C. Helton ◽  
A. J. Weir ◽  
J. A. Whitsett ◽  
T. R. Korfhagen
Keyword(s):  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Transgenic Mice ◽  
Blood Vessels ◽  
Lung Parenchyma ◽  
Lung Maturation ◽  
Alveolar Air ◽  
Parenchymal Tissue ◽  
Air Space ◽  
Conducting Airways

A wide variety of growth factors are thought to be involved in the regulation of pre- and postnatal lung maturation, including factors which bind to the epidermal growth factor receptor. Marked pulmonary fibrosis and enlarged alveolar air spaces have been observed in lungs of transgenic mice expressing human TGF-α under control of the 3.7 KB human SP-C promoter. To test whether TGF-α alters lung morphogenesis and cellular differentiation, we examined morphometrically the lungs of adult (6-10 months) mice derived from line 28, which expresses the highest level of human TGF-α transcripts among transgenic lines. Total volume of lungs (LV) fixed by airway infusion at standard pressure was similar in transgenics and aged-matched non-transgenic mice (Fig. 1). Intrapulmonary bronchi and bronchioles made up a smaller percentage of LV in transgenics than in non-transgenics (Fig. 2). Pulmonary arteries and pulmonary veins were a smaller percentage of LV in transgenic mice than in non-transgenics (Fig. 3). Lung parenchyma (lung tissue free of large vessels and conducting airways) occupied a larger percentage of LV in transgenics than in non-transgenics (Fig. 4). The number of generations of branching in conducting airways was significantly reduced in transgenics as compared to non-transgenic mice. Alveolar air space size, as measured by mean linear intercept, was almost twice as large in transgenic mice as in non-transgenics, especially when different zones within the lung were compared (Fig. 5). Alveolar air space occupied a larger percentage of the lung parenchyma in transgenic mice than in non-transgenic mice (Fig. 6). Collagen abundance was estimated in histological sections as picro-Sirius red positive material by previously-published methods. In intrapulmonary conducting airways, collagen was 4.8% of the wall in transgenics and 4.5% of the wall in non-transgenic mice. Since airways represented a smaller percentage of the lung in transgenics, the volume of interstitial collagen associated with airway wall was significantly less. In intrapulmonary blood vessels, collagen was 8.9% of the wall in transgenics and 0.7% of the wall in non-transgenics. Since blood vessels were a smaller percentage of the lungs in transgenics, the volume of collagen associated with the walls of blood vessels was five times greater. In the lung parenchyma, collagen was 51.5% of the tissue volume in transgenics and 21.2% in non-transgenics. Since parenchyma was a larger percentage of lung volume in transgenics, but the parenchymal tissue was a smaller percent of the volume, the volume of collagen associated with parenchymal tissue was only slightly greater. We conclude that overexpression of TGF-α during lung maturation alters many aspects of lung development, including branching morphogenesis of the airways and vessels and alveolarization in the parenchyma. Further, the increases in visible collagen previously associated with pulmonary fibrosis due to the overexpression of TGF-α are a result of actual increases in amounts of collagen and in a redistribution of collagen within compartments which results from morphogenetic changes. These morphogenetic changes vary by lung compartment. Supported by HL20748, ES06700 and the Cystic Fibrosis Foundation.

Methacholine-induced bronchoconstriction in dogs: effects of lung volume and O3 exposure

1988 ◽  
Vol 65 (6) ◽  
pp. 2679-2686 ◽  
Author(s):  
S. T. Kariya ◽  
S. A. Shore ◽  
W. A. Skornik ◽  
K. Anderson ◽  
R. H. Ingram ◽  
...  
Keyword(s):  
Lung Volume ◽  
Maximal Response ◽  
Maximal Effect ◽  
Response Curves ◽  
Lung Volumes ◽  
Before And After ◽  
Residual Capacity ◽  
Induced Changes ◽  
Conducting Airways ◽  
Concentration Response Curve

The maximal effect induced by methacholine (MCh) aerosols on pulmonary resistance (RL), and the effects of altering lung volume and O3 exposure on these induced changes in RL, was studied in five anesthetized and paralyzed dogs. RL was measured at functional residual capacity (FRC), and lung volumes above and below FRC, after exposure to MCh aerosols generated from solutions of 0.1-300 mg MCh/ml. The relative site of response was examined by magnifying parenchymal [RL with large tidal volume (VT) at fast frequency (RLLS)] or airway effects [RL with small VT at fast frequency (RLSF)]. Measurements were performed on dogs before and after 2 h of exposure to 3 ppm O3. MCh concentration-response curves for both RLLS and RLSF were sigmoid shaped. Alterations in mean lung volume did not alter RLLS; however, RLSF was larger below FRC than at higher lung volumes. Although O3 exposure resulted in small leftward shifts of the concentration-response curve for RLLS, the airway dominated index of RL (RLSF) was not altered by O3 exposure, nor was the maximal response using either index of RL. These data suggest O3 exposure does not affect MCh responses in conducting airways; rather, it affects responses of peripheral contractile elements to MCh, without changing their maximal response.

scholarly journals Immunolocalization of Sonic Hedgehog (Shh) in Developing Mouse Lung

2001 ◽  
Vol 49 (12) ◽  
pp. 1593-1603 ◽  
Author(s):  
Leigh-Anne D. Miller ◽  
Susan E. Wert ◽  
Jeffrey A. Whitsett
Keyword(s):  
Epithelial Cells ◽  
Sonic Hedgehog ◽  
Normal Development ◽  
Clara Cell ◽  
Mouse Lung ◽  
Lung Hypoplasia ◽  
Hepatocyte Nuclear Factor ◽  
Clara Cells ◽  
Lung Morphogenesis ◽  
Conducting Airways

Expression of sonic hedgehog (Shh) is required for normal development of the lung during embryogenesis. Loss of Shh expression in mice results in tracheoesophageal fistula, lung hypoplasia, and abnormal lung lobulation. To determine whether Shh may play a role later in lung morphogenesis, immunostaining for Shh was performed in mouse lung from embryonic day (E) 10.5 to postnatal day (PD) 24. Shh was detected in the distal epithelium of the developing mouse lung from E10.5 to E16.5. From E16.5 until PD15, Shh was present in epithelial cells in both the peripheral and conducting airways. Although all cells of the developing epithelium uniformly expressed Shh at E10.5, Shh expression was restricted to subsets of epithelial cells by E16.5. Between E16.5 and PD15, non-uniform Shh staining of epithelial cells was observed in the conducting airways in a pattern consistent with the distribution of non-ciliated bronchiolar cells (i.e., Clara cells) and the Clara cell marker CCSP. Shh did not co-localize with hepatocyte nuclear factor/forkhead homologue-4 (HFH-4), β-tubulin, or with the presence of cilia. These results support the concept that Shh plays a distinct regulatory role in the lung later in morphogenesis, when it may influence formation or cytodifferentiation of the conducting airways.

Morphology of the distal conducting airways in rhesus monkey lungs

1985 ◽  
Vol 211 (3) ◽  
pp. 295-303 ◽  
Author(s):  
Nancy K. Tyler ◽  
Charles G. Plopper
Keyword(s):  
Rhesus Monkey ◽  
Conducting Airways

scholarly journals Histopathology ofBordetella pertussisin the Baboon Model

2018 ◽  
Vol 86 (11) ◽  
Author(s):  
Lindsey I. Zimmerman ◽  
James F. Papin ◽  
Jason Warfel ◽  
Roman F. Wolf ◽  
Stanley D. Kosanke ◽  
...  
Keyword(s):  
Severe Disease ◽  
Clinical Signs ◽  
Human Infant ◽  
Mucus Production ◽  
Content Type ◽  
Age Related ◽  
Baboon Model ◽  
Relevant Animal Model ◽  
Significant Pathology ◽  
Conducting Airways

ABSTRACTPertussis is a severe respiratory disease caused byBordetella pertussis. The classic symptoms of pertussis include paroxysmal coughing with an inspiratory whoop, posttussive vomiting, cyanosis, and persistent coryzal symptoms. Infants under 2 months of age experience more severe disease, with most deaths occurring in this age group. Most of what is known about the pathology of pertussis in humans is from the evaluation of fatal human infant cases. The baboon model of pertussis provides the opportunity to evaluate the histopathology of severe but nonfatal pertussis. The baboon model recapitulates the characteristic clinical signs of pertussis observed in humans, including leukocytosis, paroxysmal coughing, mucus production, heavy colonization of the airway, and transmission of the bacteria between hosts. As in humans, baboons demonstrate age-related differences in clinical presentation, with younger animals experiencing more severe disease. We examined the histopathology of 5- to 6-week-old baboons, with the findings being similar to those reported for fatal human infant cases. In juvenile baboons, we found that the disease is highly inflammatory and concentrated to the lungs with signs of disease that would typically be diagnosed as acute respiratory distress syndrome (ARDS) and bronchopneumonia. In contrast, no significant pathology was observed in the trachea. Histopathological changes in the trachea were limited to cellular infiltrates and mucus production. Immunohistostaining revealed that the bacteria were localized to the surface of the ciliated epithelium in the conducting airways. Our observations provide important insights into the pathology of pertussis in typical, severe but nonfatal pertussis cases in a very relevant animal model.

Convective and diffusive gas transport in canine intrapulmonary airways

1992 ◽  
Vol 72 (4) ◽  
pp. 1557-1562 ◽  
Author(s):  
H. Schulz ◽  
P. Heilmann ◽  
A. Hillebrecht ◽  
J. Gebhart ◽  
M. Meyer ◽  
...  
Keyword(s):  
Dead Space ◽  
Gas Transport ◽  
Inert Gases ◽  
Differential Analysis ◽  
Mechanically Ventilated ◽  
Convective Mixing ◽  
Conducting Airways ◽  
And Diffusion ◽  
Residual Air ◽  
Space Dispersion

The significance of convective and diffusive gas transport in the respiratory system was assessed from the response of combined inert gas and particle boluses inhaled into the conducting airways. Particles, considered as “nondiffusing gas,” served as tracers for convection and two inert gases with widely different diffusive characteristics (He and SF6) as tracers for convection and diffusion. Six-milliliter boluses labeled with monodisperse di-2-ethylhexyl sebacate droplets of 0.86-microns aerodynamic diameter, 2% He, and 2% SF6 were inspired by three anesthetized mechanically ventilated beagle dogs to volumetric lung depths up to 170 ml. Mixing between inspired and residual air caused dispersion of the inspired bolus, which was quantified in terms of the bolus half-width. Dispersion of particles increased with increasing lung depth to which the boluses were inhaled. The increase followed a power law with exponents less than 0.5 (mean 0.39), indicating that the effect of convective mixing per unit volume was reduced with depth. Within the pulmonary dead space, the behavior of the inert gases He and SF6 was similar to that of the particles, suggesting that gas transport was almost solely due to convection. Beyond the dead space, dispersion of He and SF6 increased more rapidly than dispersion of particles, indicating that diffusion became significant. The gas and particle bolus technique offers a suitable approach to differential analysis of gas transport in intrapulmonary airways of lungs.

scholarly journals Cellular tropism of SARS-CoV-2 in the respiratory tract of Syrian hamsters and B6.Cg-Tg(K18-ACE2)2Prlmn/J transgenic mice

2021 ◽  
pp. 030098582110430
Author(s):  
Hui-Ling Yen ◽  
Sophie Valkenburg ◽  
Sin Fun Sia ◽  
Ka Tim Choy ◽  
J. S. Malik Peiris ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Lung Parenchyma ◽  
Productive Infection ◽  
Type I ◽  
Syrian Hamsters ◽  
Transmission Electron ◽  
Type Ii Pneumocytes ◽  
Viral Particles ◽  
Cellular Tropism ◽  
Conducting Airways

Several animal models have been developed to study the pathophysiology of SARS-CoV-2 infection and to evaluate vaccines and therapeutic agents for this emerging disease. Similar to infection with SARS-CoV-1, infection of Syrian hamsters with SARS-CoV-2 results in moderate respiratory disease involving the airways and lung parenchyma but does not lead to increased mortality. Using a combination of immunohistochemistry and transmission electron microscopy, we showed that the epithelium of the conducting airways of hamsters was the primary target for viral infection within the first 5 days of infection, with little evidence of productive infection of pneumocytes. At 6 days postinfection, antigen was cleared but parenchymal damage persisted, and the major pathological changes resolved by day 14. These findings are similar to those previously reported for hamsters with SARS-CoV-1 infection. In contrast, infection of K18-hACE2 transgenic mice resulted in pneumocyte damage, with viral particles and replication complexes in both type I and type II pneumocytes together with the presence of convoluted or cubic membranes; however, there was no evidence of virus replication in the conducting airways. The Syrian hamster is a useful model for the study of SARS-CoV-2 transmission and vaccination strategies, whereas infection of the K18-hCE2 transgenic mouse results in lethal disease with fatal neuroinvasion but with sparing of conducting airways.

Longitudinal distribution of O3 absorption in the lung: gender differences and intersubject variability

1996 ◽  
Vol 81 (4) ◽  
pp. 1651-1657 ◽  
Author(s):  
Michele L. Bush ◽  
Patrick T. Asplund ◽  
Kristen A. Miles ◽  
Abdellaziz Ben-Jebria ◽  
James S. Ultman
Keyword(s):  
Gender Differences ◽  
Dead Space ◽  
Ambient Air ◽  
Exposure Dose ◽  
Longitudinal Distribution ◽  
Exposure Condition ◽  
Intersubject Variability ◽  
Quiet Breathing ◽  
Mass Transfer Parameter ◽  
Conducting Airways

Bush, Michele L., Patrick T. Asplund, Kristen A. Miles, Abdellaziz Ben-Jebria, and James S. Ultman. Longitudinal distribution of O3 absorption in the lung: gender differences and intersubject variability. J. Appl. Physiol. 81(4): 1651–1657, 1996.—Because the National Ambient Air Quality Standard for ozone (O3) is intended to protect the most sensitive individuals in the general population, it is necessary to identify sources of intersubject variation in the exposure-dose-response cascade. We hypothesize that differences in lung anatomy can modulate exposure-dose relationships between individuals, and this results in differences between their responsiveness to O3 at a fixed exposure condition. During quiet breathing, the conducting airways remove the majority of inhaled O3, so the volume of this region should have an important impact on O3 dose distribution. Employing the bolus inhalation method, we measured the distribution of O3 absorption with respect to penetration volume (VP), and using the Fowler single-breath N2washout method, we determined the dead space volume (Vd) in the lungs of 10 men and 10 women at a fixed respiratory flow of 250 ml/s. On average, the women absorbed O3 at smaller VP than the men, and the women had smaller Vd than the men. When expressed in terms of VP/ Vd, the absorption distribution of the men and women was indistinguishable. Moreover, an interpretation of the O3 distribution in terms of an intrinsic mass transfer parameter ( Ka) indicated that differences between the O3 dosimetry in all subjects, whether men or women, could be explained by a unique correlation with anatomic dead space: Ka (in s−1) = 610 Vd −1.05(in ml). Application of this result to measurements of O3 exposure response indicated that previously reported gender differences may be due to a failure in properly accounting for tissue surface within the conducting airways.

scholarly journals Neuropeptide regulation of secretion and inflammation in human airway gland serous cells

2020 ◽  
Vol 55 (4) ◽  
pp. 1901386 ◽  
Author(s):  
Derek B. McMahon ◽  
Ryan M. Carey ◽  
Michael A. Kohanski ◽  
Charles C.L. Tong ◽  
Peter Papagiannopoulos ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Inflammatory Responses ◽  
Fluid Secretion ◽  
Antimicrobial Efficacy ◽  
Transmembrane Conductance Regulator ◽  
Cytokine Release ◽  
Transmembrane Conductance ◽  
Mucus Rheology ◽  
Peptide Secretion ◽  
Conducting Airways

Airway submucosal gland serous cells are sites of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) and are important for fluid secretion in conducting airways. To elucidate how neuropeptides regulate serous cells, we tested if human nasal turbinate serous cells secrete bicarbonate (HCO3−), important for mucus polymerisation and antimicrobial peptide function, during stimulation with cAMP-elevating vasoactive intestinal peptide (VIP) and if this requires CFTR. Serous cells stimulated with VIP exhibited a ∼15–20% cAMP-dependent decrease in cell volume and a ∼0.15 unit decrease in intracellular pH (pHi), reflecting activation of Cl− and HCO3− secretion, respectively. HCO3− secretion was directly dependent on CFTR and was absent in cells from CF patients. In contrast, neuropeptide Y (NPY) reduced VIP-evoked cAMP increases, CFTR activation, and Cl−/HCO3− secretion. Culture of primary serous cells in a model that maintained a serous phenotype confirmed the activating and inhibiting effects of VIP and NPY, respectively, on fluid and HCO3− secretion. Moreover, VIP enhanced antimicrobial peptide secretion and antimicrobial efficacy of secretions while NPY reduced antimicrobial efficacy. In contrast, NPY enhanced cytokine release while VIP reduced cytokine release through a mechanism requiring CFTR. As levels of VIP and NPY are up-regulated in diseases like allergy, asthma, and chronic rhinosinusitis, the balance of these two peptides in the airway may control mucus rheology and inflammatory responses in serous cells. Furthermore, the loss of CFTR conductance in serous cells may contribute to CF pathophysiology by increasing serous cells inflammatory responses in addition to directly impairing Cl− and HCO3− secretion.

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