Hyperoxia combined with high tidal volume mechanical ventilation reduces alveolar type II cell adhesion: reduced phosphorylation of focal adhesion proteins and effect of KGF

2006 ◽  
Vol 39 ◽  
pp. S595
Author(s):  
C.M. Waters ◽  
L.P. Desai ◽  
S.E. Sinclair ◽  
A. Hassid ◽  
K.E. Chapman
Keyword(s):  
Mechanical Ventilation ◽  
Cell Adhesion ◽  
Tidal Volume ◽  
Focal Adhesion ◽  
Alveolar Type ◽  
Type Ii ◽  
Adhesion Proteins ◽  
Alveolar Type Ii Cell ◽  
Focal Adhesion Proteins ◽  
Type Ii Cell

High tidal volume mechanical ventilation with hyperoxia alters alveolar type II cell adhesion

2007 ◽  
Vol 293 (3) ◽  
pp. L769-L778 ◽  
Author(s):  
Leena P. Desai ◽  
Scott E. Sinclair ◽  
Kenneth E. Chapman ◽  
Aviv Hassid ◽  
Christopher M. Waters
Keyword(s):  
Mechanical Ventilation ◽  
Cell Adhesion ◽  
Tidal Volume ◽  
Focal Adhesion ◽  
Keratinocyte Growth Factor ◽  
Dominant Negative ◽  
High Tidal Volume ◽  
Alveolar Type ◽  
Type Ii ◽  
And Migration

Patients with acute respiratory distress syndrome undergoing mechanical ventilation may be exposed to both high levels of stretch and high levels of oxygen. We hypothesized that the combination of high stretch and hyperoxia promotes loss of epithelial adhesion and impairs epithelial repair mechanisms necessary for restoration of barrier function. We utilized a model of high tidal volume mechanical ventilation (25 ml/kg) with hyperoxia (50% O2) in rats to investigate alveolar type II (AT2) cell adhesion and focal adhesion signaling. AT2 cells isolated from rats exposed to hyperoxia and high tidal volume mechanical ventilation (MVHO) exhibited significantly decreased cell adhesion and reduction in phosphotyrosyl levels of focal adhesion kinase (FAK) and paxillin compared with control rats, rats exposed to hyperoxia without ventilation (HO), or rats ventilated with normoxia (MV). MV alone increased phosphorylation of p130Cas. RhoA activation was increased by MV, HO, and the combination of MV and HO. Treatment of MVHO cells with keratinocyte growth factor (KGF) for 1 h upon isolation reduced RhoA activity and restored attachment to control levels. Attachment and migration of control AT2 cells was significantly decreased by constitutively active RhoA or a kinase inactive form of FAK (FRNK), whereas expression of dominant negative RhoA in cells from MVHO-treated rats restored cell adhesion. Mechanical ventilation with hyperoxia promotes changes in focal adhesion proteins and RhoA in AT2 cells that may be deleterious for cell adhesion and migration.

Alveolar Type II Cell Na, K-ATPase is Upregulated During Mechanical Ventilation-induced Pulmonary Edema

CHEST Journal ◽  
1994 ◽  
Vol 105 (3) ◽  
pp. 116S-117S ◽  
Author(s):  
J. Lasha Sznajder ◽  
Karen M. Ridge ◽  
Z. Leah Harris ◽  
Walter Olivera ◽  
Clara Curiel ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Pulmonary Edema ◽  
Alveolar Type ◽  
Type Ii ◽  
Alveolar Type Ii Cell ◽  
Type Ii Cell

scholarly journals Covid-19 Interstitial Pneumonia: Histological and Immunohistochemical Features on Cryobiopsies

Respiration ◽  
2021 ◽  
pp. 369-379
Author(s):  
Claudio Doglioni ◽  
Claudia Ravaglia ◽  
Marco Chilosi ◽  
Giulio Rossi ◽  
Alessandra Dubini ◽  
...  
Keyword(s):  
Interstitial Pneumonia ◽  
Diffuse Alveolar Damage ◽  
Alveolar Type ◽  
Type Ii ◽  
Cell Hyperplasia ◽  
Nuclear Expression ◽  
Alveolar Type Ii Cell ◽  
Hyaline Membranes ◽  
Type Ii Cell ◽  
Phosphorylated Stat3

Background: The pathogenetic steps leading to Covid-19 interstitial pneumonia remain to be clarified. Most postmortem studies to date reveal diffuse alveolar damage as the most relevant histologic pattern. Antemortem lung biopsy may however provide more precise data regarding the earlier stages of the disease, providing a basis for novel treatment approaches. Objectives: To ascertain the morphological and immunohistochemical features of lung samples obtained in patients with moderate Covid-19 pneumonia. Methods: Transbronchial lung cryobiopsy was carried out in 12 Covid-19 patients within 20 days of symptom onset. Results: Histopathologic changes included spots of patchy acute lung injury with alveolar type II cell hyperplasia, with no evidence of hyaline membranes. Strong nuclear expression of phosphorylated STAT3 was observed in >50% of AECII. Interalveolar capillaries showed enlarged lumen and were in part arranged in superposed rows. Pulmonary venules were characterized by luminal enlargement, thickened walls, and perivascular CD4+ T-cell infiltration. A strong nuclear expression of phosphorylated STAT3, associated with PD-L1 and IDO expression, was observed in endothelial cells of venules and interstitial capillaries. Alveolar spaces macrophages exhibited a peculiar phenotype (CD68, CD11c, CD14, CD205, CD206, CD123/IL3AR, and PD-L1). Conclusions: Morphologically distinct features were identified in early stages of Covid-19 pneumonia, with epithelial and endothelial cell abnormalities different from either classical interstitial lung diseases or diffuse alveolar damage. Alveolar type II cell hyperplasia was a prominent event in the majority of cases. Inflammatory cells expressed peculiar phenotypes. No evidence of hyaline membranes and endothelial changes characterized by IDO expression might in part explain the compliance and the characteristic pulmonary vasoplegia observed in less-advanced Covid-19 pneumonia.

Quantitative Analysis of Alveolar Type II Cell Tumors in Mice by Whole Lung Serial and Step Sections

1989 ◽  
Vol 17 (4_part_2) ◽  
pp. 737-742 ◽  
Author(s):  
Sabine Rehm ◽  
Jerrold M. Ward
Keyword(s):  
Mouse Lung ◽  
Alveolar Type ◽  
Type Ii ◽  
Serial Sections ◽  
Feasible Method ◽  
Alveolar Type Ii Cell ◽  
Microscopic Lesion ◽  
Entire Lung ◽  
Type Ii Cell ◽  
Mouse Lungs

Alveolar type II cell tumors were induced transplacentally by intraperitoneal injection of pregnant C3H/HeNCr MTV– or Swiss Webster mice with N-nitrosoethylurea at a dose of 0.5 mmol/kg and 0.74 mmol/kg. At different time points after birth (1–32 weeks), the entire lungs from 40 of the male offspring were inflated with Bouin's fixative, separated into lobes, and sectioned at 5 μm serially to detect every microscopic lesion. Results were compared with those obtained from examining only every 10th, 20th, or a single mid-level section from the same material. On average, 150 serial sections were prepared per mouse lung. Initially, only purely solid/alveolar or purely tubulopapillary types were observed but with tumor progression, papillary structures developed within solid tumors resulting in mixed neoplasms. Analyzing mouse lungs in step sections of every 10th section (50–60 μm), 5/238 (2%) of the tumors were missed, in step sections of every 20th section (100–120 μm), 16/238 (7%) of the tumors were not detected and usually less than half of the tumors were seen in the single mid-level section. The approximate size of the neoplasms is indicated by the total number of sections per tumor. The dimensions of tumors evaluated with step sections of 10 or 20 were comparable to the size observed with serial sections. It is concluded that the evaluation of mouse lung tumors in steps of approximately 50 μm is basically equivalent to the study of serial sections and appears to be a feasible method to assess the complete incidence, histological type, and size of all proliferative processes throughout the entire lung.

scholarly journals Effects of Fas-Ligand Overexpression on Alveolar Type II Cell Growth Kinetics in Perinatal Murine Lungs

2010 ◽  
Vol 68 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Monique E de Paepe ◽  
Sheila A Haley ◽  
Zacharie Lacourse ◽  
Quanfu Mao
Keyword(s):  
Cell Growth ◽  
Growth Kinetics ◽  
Fas Ligand ◽  
Alveolar Type ◽  
Type Ii ◽  
Alveolar Type Ii Cell ◽  
Type Ii Cell ◽  
Cell Growth Kinetics

Cytotoxic effects of cigarette smoke extract on an alveolar type II cell-derived cell line

2001 ◽  
Vol 281 (2) ◽  
pp. L509-L516 ◽  
Author(s):  
Yuma Hoshino ◽  
Tadashi Mio ◽  
Sonoko Nagai ◽  
Hiroyuki Miki ◽  
Isao Ito ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Line ◽  
Cigarette Smoke ◽  
A549 Cells ◽  
Cigarette Smoke Extract ◽  
Alveolar Type ◽  
Type Ii ◽  
Cytotoxic Effects ◽  
Alveolar Type Ii Cell ◽  
Type Ii Cell

Injury of the alveolar epithelium by cigarette smoke is presumed to be an important process in the pathogenesis of smoking-related pulmonary diseases. We investigated the cytotoxic effects of cigarette smoke extract (CSE) on an alveolar type II cell-derived cell line (A549). CSE caused apoptosis at concentrations of 5% or less and necrosis at 10% or more. When CSE was exposed to air before application to A549 cells, the cytotoxic effects were attenuated. CSE caused cell death without direct contact with the cells. Acrolein and hydrogen peroxide, two major volatile factors in cigarette smoke, caused cell death in a similar manner. Aldehyde dehydrogenase, a scavenger of aldehydes, and N-acetylcysteine, a scavenger of oxidants and aldehydes, completely inhibited CSE-induced apoptosis. CSE and acrolein increased intracellular oxidant activity. In conclusion, apoptosis of alveolar epithelial cells may be one of the mechanisms of lung injury induced by cigarette smoking. This cytotoxic effect might be due to an interaction between aldehydes and oxidants present in CSE or formed in CSE-exposed cells.

Ontogeny of gamma-glutamyltransferase in the rat lung

1997 ◽  
Vol 272 (4) ◽  
pp. L739-L744 ◽  
Author(s):  
S. M. Oakes ◽  
Y. Takahashi ◽  
M. C. Williams ◽  
M. Joyce-Brady
Keyword(s):  
Enzyme Activity ◽  
Clara Cell ◽  
Glutathione Metabolism ◽  
Alveolar Type ◽  
Type Ii ◽  
Rat Lung ◽  
Gamma Glutamyltransferase ◽  
Adult Lung ◽  
Alveolar Type Ii Cell ◽  
Type Ii Cell

gamma-Glutamyltransferase (gamma-GT) is a key enzyme in the metabolism of glutathione and glutathione-substituted molecules. The gamma-GT gene is expressed in two epithelial cells of the adult lung, the bronchiolar Clara cell and the alveolar type II cell. Because pulmonary glutathione metabolism may be important in the perinatal period, we studied gamma-GT ontogeny in the developing rat lung. In the late fetal and early postnatal lung, gamma-GT mRNA was below detectable limits on Northern blots. Pulmonary gamma-GT protein and enzyme activity were present at low levels after fetal day 18. gamma-GT protein appeared as a high-molecular-mass band (>95 kDa), with small amounts of enzymatically active gamma-GT heterodimer. Between the 2nd and 3rd postnatal wk, pulmonary gamma-GT mRNA expression increased in association with an increase in gamma-GT protein and enzyme activity that reached adult lung levels. At this time, gamma-GT protein appeared predominantly in the heterodimeric form with small amounts of the >95-kDa protein. Immunocytochemistry revealed that, in the fetal and early postnatal lung, gamma-GT was expressed only in the alveolar type II cell, whereas the Clara cell became the major site of gamma-GT mRNA and protein expression by 2-3 wk and in the adult. Type II cells isolated from the fetal lung express gamma-GT mRNA and synthesize the >95-kDa form of gamma-GT in excess of the heterodimer. These studies demonstrate that the alveolar type II cell is the only cell producing gamma-GT in the newborn lung and that it synthesizes a form of gamma-GT that appears to differ from that produced at a later time point by the Clara cell.

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