scholarly journals Electron Microscopic Study of the Phagocytosis Process in Lung

1960 ◽  
Vol 7 (2) ◽  
pp. 357-366 ◽  
Author(s):  
H. E. Karrer
Keyword(s):  
Plasma Membrane ◽  
Alveolar Macrophages ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Electron Microscopic ◽  
Double Line ◽  
Alveolar Epithelial ◽  
Culture Cells ◽  
India Ink ◽  
Intracellular Vesicles

Diluted India ink was instilled into the nasal cavity of mice and the lungs of some animals were fixed with osmium tetroxide at various intervals after one instillation. The lungs of other animals were fixed after 4, 7, 9, 16, or 18 daily instillations. The India ink was found to be phagocytized almost exclusively by the free alveolar macrophages. A few particles are occasionally seen within thin portions of alveolar epithelium, within the "small" alveolar epithelial cells, or within occasional leukocytes in the lumina of alveoli. The particles are ingested by an invagination process of the plasma membrane resulting in the formation of intracellular vesicles and vacuoles. Ultimately large amounts of India ink accumulate in the cell, occupying substantial portions of the cytoplasm. The surfaces of phagocytizing macrophages show signs of intense motility. Their cytoplasm contains numerous particles, resembling Palade particles, and a large amount of rough surfaced endoplasmic reticulum. These structures are interpreted as indicative of protein synthesis. At the level of resolution achieved in this study the membranes of this reticulum appear as single dense "lines." On the other hand, the plasma membrane and the limiting membranes of vesicles and of vacuoles often exhibit the double-line structure typical of unit membranes (Robertson, 37). The inclusion bodies appear to be the product of phagocytosis. It is believed that some of them derive from the vacuoles mentioned above, and that they correspond to similar structures seen in phase contrast cinemicrographs of culture cells. Their matrix represents phagocytized material. Certain structures within this matrix are considered as secondary and some of these structures possess an ordered form probably indicative of the presence of lipid. The possible origin and the fate of alveolar macrophages are briefly discussed.

scholarly journals Linking Fibrotic Remodeling and Ultrastructural Alterations of Alveolar Epithelial Cells after Deletion of Nedd4-2

2021 ◽  
Vol 22 (14) ◽  
pp. 7607
Author(s):  
Theresa A. Engelmann ◽  
Lars Knudsen ◽  
Dominik H. W. Leitz ◽  
Julia Duerr ◽  
Michael F. Beers ◽  
...  
Keyword(s):  
Surface Area ◽  
Alveolar Epithelium ◽  
Cell Ultrastructure ◽  
Alveolar Epithelial Cells ◽  
Electron Microscopic Level ◽  
Type I ◽  
Electron Microscopic ◽  
Septal Wall ◽  
Ultrastructural Alterations ◽  
Alveolar Epithelial

Our previous study showed that in adult mice, conditional Nedd4-2-deficiency in club and alveolar epithelial type II (AE2) cells results in impaired mucociliary clearance, accumulation of Muc5b and progressive, terminal pulmonary fibrosis within 16 weeks. In the present study, we investigated ultrastructural alterations of the alveolar epithelium in relation to interstitial remodeling in alveolar septa as a function of disease progression. Two, eight and twelve weeks after induction of Nedd4-2 knockout, lungs were fixed and subjected to design-based stereological investigation at the light and electron microscopic level. Quantitative data did not show any abnormalities until 8 weeks compared to controls. At 12 weeks, however, volume of septal wall tissue increased while volume of acinar airspace and alveolar surface area significantly decreased. Volume and surface area of alveolar epithelial type I cells were reduced, which could not be compensated by a corresponding increase of AE2 cells. The volume of collagen fibrils in septal walls increased and was linked with an increase in blood–gas barrier thickness. A high correlation between parameters reflecting interstitial remodeling and abnormal AE2 cell ultrastructure could be established. Taken together, abnormal regeneration of the alveolar epithelium is correlated with interstitial septal wall remodeling.

scholarly journals Epithelial–Mesenchymal Transition in the Pathogenesis of Idiopathic Pulmonary Fibrosis

Medicina ◽  
2019 ◽  
Vol 55 (4) ◽  
pp. 83 ◽  
Author(s):  
Francesco Salton ◽  
Maria Volpe ◽  
Marco Confalonieri
Keyword(s):  
Epithelial Cells ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Treatment Options ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Serious Disease

Idiopathic pulmonary fibrosis (IPF) is a serious disease of the lung, which leads to extensive parenchymal scarring and death from respiratory failure. The most accepted hypothesis for IPF pathogenesis relies on the inability of the alveolar epithelium to regenerate after injury. Alveolar epithelial cells become apoptotic and rare, fibroblasts/myofibroblasts accumulate and extracellular matrix (ECM) is deposited in response to the aberrant activation of several pathways that are physiologically implicated in alveologenesis and repair but also favor the creation of excessive fibrosis via different mechanisms, including epithelial–mesenchymal transition (EMT). EMT is a pathophysiological process in which epithelial cells lose part of their characteristics and markers, while gaining mesenchymal ones. A role for EMT in the pathogenesis of IPF has been widely hypothesized and indirectly demonstrated; however, precise definition of its mechanisms and relevance has been hindered by the lack of a reliable animal model and needs further studies. The overall available evidence conceptualizes EMT as an alternative cell and tissue normal regeneration, which could open the way to novel diagnostic and prognostic biomarkers, as well as to more effective treatment options.

Silica directly increases permeability of alveolar epithelial cells

1990 ◽  
Vol 68 (4) ◽  
pp. 1354-1359 ◽  
Author(s):  
R. K. Merchant ◽  
M. W. Peterson ◽  
G. W. Hunninghake
Keyword(s):  
Epithelial Cells ◽  
Cell Injury ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Dependent Manner ◽  
Alveolar Epithelial ◽  
Lactate Dehydrogenase Release ◽  
Capillary Membrane

Alveolar epithelial cell injury and increased alveolar-capillary membrane permeability are important features of acute silicosis. To determine whether silica particles contribute directly to this increased permeability, we measured paracellular permeability of rat alveolar epithelium after exposure to silica, in vitro, using markers of the extracellular space. Silica (Minusil) markedly increased permeability in a dose- and time-dependent manner. This was not the result of cytolytic injury, because lactate dehydrogenase release from monolayers exposed to silica was not increased. Pretreatment of the silica with serum, charged dextrans, or aluminum sulfate blocked the increase in permeability. Scanning electron microscopy demonstrated adherence of the silica to the surface of the alveolar epithelial cells. Thus silica can directly increase permeability of alveolar epithelium.

scholarly journals Mechanisms of EGF-induced stimulation of sodium reabsorption by alveolar epithelial cells

1998 ◽  
Vol 275 (1) ◽  
pp. C82-C92 ◽  
Author(s):  
Spencer I. Danto ◽  
Zea Borok ◽  
Xiao-Ling Zhang ◽  
Melissa Z. Lopez ◽  
Paryus Patel ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Cell Labeling ◽  
Northern Analysis ◽  
Sodium Reabsorption ◽  
Alveolar Epithelial ◽  
Subunit Mrna ◽  
Epidermal Growth ◽  
Stimulation Of

We investigated the effects of epidermal growth factor (EGF) on active Na+ absorption by alveolar epithelium. Rat alveolar epithelial cells (AEC) were isolated and cultivated in serum-free medium on tissue culture-treated polycarbonate filters. mRNA for rat epithelial Na+ channel (rENaC) α-, β-, and γ-subunits and Na+ pump α1- and β1-subunits were detected in day 4 monolayers by Northern analysis and were unchanged in abundance in day 5 monolayers in the absence of EGF. Monolayers cultivated in the presence of EGF (20 ng/ml) for 24 h from day 4 to day 5 showed an increase in both α1 and β1Na+ pump subunit mRNA but no increase in rENaC subunit mRNA. EGF-treated monolayers showed parallel increases in Na+ pump α1- and β1-subunit protein by immunoblot relative to untreated monolayers. Fixed AEC monolayers demonstrated predominantly membrane-associated immunofluorescent labeling with anti-Na+ pump α1- and β1-subunit antibodies, with increased intensity of cell labeling for both subunits seen at 24 h following exposure to EGF. These changes in Na+ pump mRNA and protein preceded a delayed (>12 h) increase in short-current circuit (measure of active transepithelial Na+transport) across monolayers treated with EGF compared with untreated monolayers. We conclude that EGF increases active Na+ resorption across AEC monolayers primarily via direct effects on Na+ pump subunit mRNA expression and protein synthesis, leading to increased numbers of functional Na+ pumps in the basolateral membranes.

scholarly journals Characterization of Early Stages of Human Alveolar Infection by the Q Fever AgentCoxiella burnetii

2019 ◽  
Vol 87 (5) ◽  
Author(s):  
Amanda L. Dragan ◽  
Richard C. Kurten ◽  
Daniel E. Voth
Keyword(s):  
Epithelial Cells ◽  
Lung Tissue ◽  
Alveolar Macrophages ◽  
Human Lung ◽  
Q Fever ◽  
Cell Types ◽  
Alveolar Epithelial Cells ◽  
Human Lung Tissue ◽  
Content Type ◽  
Alveolar Epithelial

ABSTRACTHuman Q fever is caused by the intracellular bacterial pathogenCoxiella burnetii. Q fever presents with acute flu-like and pulmonary symptoms or can progress to chronic, severe endocarditis. After human inhalation,C. burnetiiis engulfed by alveolar macrophages and transits through the phagolysosomal maturation pathway, resisting the acidic pH of lysosomes to form a parasitophorous vacuole (PV) in which to replicate. Previous studies showed thatC. burnetiireplicates efficiently in primary human alveolar macrophages (hAMs) inex vivohuman lung tissue. AlthoughC. burnetiireplicates in most cell typesin vitro, the pathogen does not grow in non-hAM cells of human lung tissue. In this study, we investigated the interaction betweenC. burnetiiand other pulmonary cell types apart from the lung environment.C. burnetiiformed a prototypical PV and replicated efficiently in human pulmonary fibroblasts and in airway, but not alveolar, epithelial cells. Atypical PV expansion in alveolar epithelial cells was attributed in part to defective recruitment of autophagy-related proteins. Further assessment of theC. burnetiigrowth niche showed that macrophages mounted a robust interleukin 8 (IL-8), neutrophil-attracting response toC. burnetiiand ultimately shifted to an M2-polarized phenotype characteristic of anti-inflammatory macrophages. Considering our findings together, this study provides further clarity on the uniqueC. burnetii-lung dynamic during early stages of human acute Q fever.

Voltage-gated proton channels help regulate pHi in rat alveolar epithelium

2005 ◽  
Vol 288 (2) ◽  
pp. L398-L408 ◽  
Author(s):  
Ricardo Murphy ◽  
Vladimir V. Cherny ◽  
Deri Morgan ◽  
Thomas E. DeCoursey
Keyword(s):  
Epithelial Cells ◽  
Ph Regulation ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Proton Channel ◽  
Resting Cells ◽  
Proton Channels ◽  
Voltage Gated ◽  
Alveolar Epithelial

Voltage-gated proton channels are expressed highly in rat alveolar epithelial cells. Here we investigated whether these channels contribute to pH regulation. The intracellular pH (pHi) was monitored using BCECF in cultured alveolar epithelial cell monolayers and found to be 7.13 in nominally HCO3−-free solutions [at external pH (pHo) 7.4]. Cells were acid-loaded by the NH4+ prepulse technique, and the recovery was observed. Under conditions designed to eliminate the contribution of other transporters that alter pH, addition of 10 μM ZnCl2, a proton channel inhibitor, slowed recovery about twofold. In addition, the pHi minimum was lower, and the time to nadir was increased. Slowing of recovery by ZnCl2 was observed at pHo 7.4 and pHo 8.0 and in normal and high-K+ Ringer solutions. The observed rate of Zn2+-sensitive pHi recovery required activation of a small fraction of the available proton conductance. We conclude that proton channels contribute to pHi recovery after an acid load in rat alveolar epithelial cells. Addition of ZnCl2 had no effect on pHi in unchallenged cells, consistent with the expectation that proton channels are not open in resting cells. After inhibition of all known pH regulators, slow pHi recovery persisted, suggesting the existence of a yet-undefined acid extrusion mechanism in these cells.

Pneumonia in Lambs Inoculated with Bordetella parapertussis: Bronchoalveolar Lavage and Ultrastructural Studies

1988 ◽  
Vol 25 (4) ◽  
pp. 297-303 ◽  
Author(s):  
W. Chen ◽  
M. R. Alley ◽  
B. W. Manktelow ◽  
D. Hopcroft ◽  
R. Bennett
Keyword(s):  
Epithelial Cells ◽  
Bronchoalveolar Lavage ◽  
Alveolar Macrophages ◽  
Bronchial Epithelium ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Bordetella Parapertussis ◽  
Alveolar Epithelial ◽  
Ultrastructural Studies ◽  
Cell Counts

Eight colostrum-deprived lambs were inoculated intratracheally with ovine isolates of Bordetella parapertussis. Fluids obtained by bronchoalveolar lavage had a large increase in total cell counts 24 hours after inoculation; up to 93% of cells were neutrophils. From 3 days after inoculation, the number of alveolar macrophages in lavage samples was markedly increased. From 5 days onwards, many alveolar macrophages had moderate to severe cytoplasmic vacuolation. Topographically, tracheal and bronchial epithelium was covered by a large amount of inflammatory exudate 24 hours after inoculation. Later, the tracheobronchial epithelium showed focal extrusions from ciliated cells, which were occasionally associated with B. parapertussis organisms. Ultrastructurally, cytopathological changes associated with B. parapertussis infection were mild focal degeneration of airway epithelium with slight loss of cilia, moderate to severe degeneration of type I and type II alveolar epithelial cells, and focal inflammation in the lungs. These results suggest that the primary targets of B. parapertussis infection are alveolar macrophages and the epithelial cells of bronchioles and alveoli.

Distinct effects of oxygen on surfactant protein B expression in bronchiolar and alveolar epithelium

1992 ◽  
Vol 262 (1) ◽  
pp. L32-L39 ◽  
Author(s):  
K. A. Wikenheiser ◽  
S. E. Wert ◽  
J. R. Wispe ◽  
M. Stahlman ◽  
M. D'Amore-Bruno ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Alveolar Epithelium ◽  
Surfactant Protein ◽  
Alveolar Epithelial Cells ◽  
Cell Protein ◽  
Altered Expression ◽  
Alveolar Epithelial ◽  
Surfactant Protein B ◽  
Bronchiolar Epithelium ◽  
Protein B

Hyperoxia causes severe lung injury in association with altered expression of surfactant proteins and lipids. To test whether oxygen induces surfactant protein B (SP-B) expression in specific respiratory epithelial cells, adult B6C3F1 and FVB/N mice were exposed to room air or 95% oxygen for 1–5 days. Northern blot analysis demonstrated an 8- to 10-fold increase in SP-B mRNA after 3 days that was maintained thereafter. In situ hybridization localized SP-B mRNA to bronchial, bronchiolar, and alveolar epithelial cells. Hyperoxia was associated with increased SP-B mRNA, noted primarily in the bronchiolar epithelium and decreased SP-B mRNA in the alveolar epithelium. After 5 days, central regions of lung parenchyma were nearly devoid of SP-B mRNA, while SP-B mRNA was maintained in alveolar cell populations close to vascular structures. To determine whether increased bronchiolar expression of SP-B mRNA during hyperoxia was a specific response, the abundance of CC10 mRNA (a Clara cell protein) was assessed. CC10 mRNA was detected in tracheal, bronchial, and bronchiolar, but not alveolar epithelium and was decreased upon exposure to hyperoxia. Immunocytochemistry demonstrated that SP-B proprotein was detected in bronchial, bronchiolar, and alveolar epithelial cells with staining increased in the bronchial and bronchiolar epithelium upon exposure to hyperoxia. SP-B gene expression in the respiratory epithelium is regulated at a pretranslational level and occurs in a cell specific manner during hyperoxic injury in the mouse.

scholarly journals Hypoxia regulates gene expression of alveolar epithelial transport proteins

2000 ◽  
Vol 88 (5) ◽  
pp. 1890-1896 ◽  
Author(s):  
Christine Clerici ◽  
Michael A. Matthay
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Alveolar Epithelium ◽  
Transport Proteins ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Type Ii ◽  
Atp Content ◽  
Glut 1 ◽  
Alveolar Epithelial

Alveolar hypoxia occurs during ascent to high altitude but is also commonly observed in many acute and chronic pulmonary disorders. The alveolar epithelium is directly exposed to decreases in O2tension, but a few studies have evaluated the effects of hypoxia on alveolar cell function. The alveolar epithelium consists of two cell types: large, flat, squamous alveolar type I and cuboidal type II (ATII). ATII cells are more numerous and have a number of critical functions, including transporting ions and substrates required for many physiological processes. ATII cells express 1) membrane proteins used for supplying substrates required for cell metabolism and 2) ion transport proteins such as Na+channels and Na+-K+-ATPase, which are involved in the vectorial transport of Na+from the alveolar to interstitial spaces and therefore drive the resorption of alveolar fluid. This brief review focuses on gene expression regulation of glucose transporters and Na+transport proteins by hypoxia in alveolar epithelial cells. Cells exposed to severe hypoxia (0% or 3% O2) for 24 h upregulate the activity and expression of the glucose transporter GLUT-1, resulting in preservation of ATP content. Hypoxia-induced increases in GLUT-1 mRNA levels are due to O2deprivation and inhibition of oxidative phosphorylation. This regulation occurs at the transcriptional level through activation of a hypoxia-inducible factor. In contrast, hypoxia downregulates expression and activity of Na+channels and Na+-K+-ATPase in cultured alveolar epithelial cells. Hypoxia induces time- and concentration-dependent decreases of α-, β-, and γ-subunits of epithelial Na+channel mRNA and β1- and α1-subunits of Na+-K+-ATPase, effects that are completely reversed after reoxygenation. The mechanisms by which O2deprivation regulates gene expression of Na+transport proteins are not fully elucidated but likely involve the redox status of the cell. Thus hypoxia regulates gene expression of transport proteins in cultured alveolar epithelial type II cells differently, preserving ATP content.

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