O2- and pneumonia-induced lung injury. II. Properties of pulmonary surfactant

1989 ◽  
Vol 67 (1) ◽  
pp. 357-365 ◽  
Author(s):  
R. J. King ◽  
J. J. Coalson ◽  
J. J. Seidenfeld ◽  
A. R. Anzueto ◽  
D. B. Smith ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Lung Injury ◽  
Pulmonary Surfactant ◽  
Phospholipid Composition ◽  
Lung Mechanics ◽  
Type Ii ◽  
Biochemical Modification ◽  
Type Ii Cell ◽  
Normal Composition ◽  
Substantial Change

Pulmonary surfactant was isolated from the lavage fluids of animals during the course of exposure to 100% O2, 80% O2, 40% O2, or 80% O2 plus 10(8) Pseudomonas aeruginosa instilled intratracheally and analyzed for its phospholipid composition. After 4–5 days of exposure to 100% O2, disaturated phophatidylcholine (DSPC) decreased to 87% of control, whereas the ratio of phosphatidylglycerol to phosphatidylinositol (PG/PI) was 37% of control. Longer periods of ventilation with 100% O2 resulted in DSPC falling to less than 40% of control. The injury was not reversed by reducing the O2 to 50%; rather, a progressive deterioration ensued. Acute respiratory failure (ARF) induced by 5 days of bacterial infection was very similar to that seen after 5 days of exposure to 100% O2. Ventilation with 80% O2 for 6 days resulted in smaller changes in DSPC but with differences in PG/PI comparable to those seen with 100% O2 or infection. We conclude that the ability of the type II cell to synthesize surfactant of normal composition is significantly impaired in these models of ARF. The earliest index of biochemical modification is the substantial change in PG/PI, which may be predictive of early lung injury. Further exacerbation of the injury could result in the reduction of DSPC content, with subsequent changes in lung mechanics and gas exchange.

scholarly journals Type I interferon promotes alveolar epithelial type II cell survival during pulmonary Streptococcus pneumoniae infection and sterile lung injury in mice

2016 ◽  
Vol 46 (9) ◽  
pp. 2175-2186 ◽  
Author(s):  
Barbara B. Maier ◽  
Anastasiya Hladik ◽  
Karin Lakovits ◽  
Ana Korosec ◽  
Rui Martins ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Lung Injury ◽  
Cell Survival ◽  
Type I Interferon ◽  
Type I ◽  
Type Ii ◽  
Alveolar Epithelial ◽  
Type Ii Cell

STAT-3 regulates surfactant phospholipid homeostasis in normal lung and during endotoxin-mediated lung injury

2008 ◽  
Vol 104 (6) ◽  
pp. 1753-1760 ◽  
Author(s):  
Machiko Ikegami ◽  
Angelica Falcone ◽  
Jeffrey A. Whitsett
Keyword(s):  
Epithelial Cells ◽  
Lung Injury ◽  
Critical Role ◽  
Lung Mechanics ◽  
Normal Lung ◽  
Type Ii Cells ◽  
Type Ii ◽  
Phospholipid Synthesis ◽  
Respiratory Epithelial Cells ◽  
Respiratory Epithelial

Acute lung injury associated with surfactant deficiency remains a major cause of pulmonary morbidity and mortality. Since signal transducer and activator of transcription-3 (STAT-3) plays an important role in protecting respiratory epithelial cells during injury, we hypothesized that STAT-3 may regulate gene expression in type II cells that mediate surfactant phospholipid synthesis. Conditional deletion of Stat-3 in respiratory epithelial cells in the lung of transgenic mice ( Stat-3Δ/Δ mice) decreased surfactant phospholipid synthesis and secretion. Deletion of Stat-3 was associated with decreased expression of Akt2, Srebf-1, and other genes expressed in type II cells that may influence surfactant phospholipid synthesis ( Glut-1, Slc34a2, Gpam, Acox2, and Cds2). Stat-3Δ/Δ mice were more susceptible to intratracheal lipopolysaccharide (LPS). Saturated phosphatidylcholine and surfactant protein B levels were significantly decreased in bronchoalveolar lavage fluid from LPS-treated Stat-3Δ/Δ mice. Alveolar capillary leak, proinflammatory cytokine expression, and perturbations of lung mechanics caused by LPS were exacerbated after deletion of STAT-3. STAT-3 plays a critical role in the regulation of surfactant lipid synthesis in the normal lung and during lung injury caused by LPS.

Late Breaking Abstract - Aging impairs alveolar epithelial type II cell function in acute lung injury

2019 ◽  
Author(s):  
Christina Brandenberger ◽  
Tolga Yazicioglu ◽  
Cheng-Kai Huang ◽  
Christian Bär ◽  
Christian Mühlfeld
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Cell Function ◽  
Type Ii ◽  
Alveolar Epithelial ◽  
Type Ii Cell

Aging causes alveolar epithelial type II cell dysfunction in acute lung injury

2020 ◽  
Author(s):  
C Brandenberger ◽  
T Yazicioglu ◽  
C Autilio ◽  
C Huang ◽  
C Bär ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Type Ii ◽  
Alveolar Epithelial ◽  
Cell Dysfunction ◽  
Type Ii Cell

scholarly journals Alveolar Type II cell transplantation restores pulmonary surfactant protein levels in lung fibrosis

2014 ◽  
Vol 33 (7) ◽  
pp. 758-765 ◽  
Author(s):  
Raquel Guillamat-Prats ◽  
Gemma Gay-Jordi ◽  
Antoni Xaubet ◽  
Victor I. Peinado ◽  
Anna Serrano-Mollar
Keyword(s):  
Cell Transplantation ◽  
Lung Fibrosis ◽  
Pulmonary Surfactant ◽  
Surfactant Protein ◽  
Alveolar Type ◽  
Type Ii ◽  
Protein Levels ◽  
Alveolar Type Ii Cell ◽  
Type Ii Cell ◽  
Pulmonary Surfactant Protein

scholarly journals Hepatocyte growth factor is elevated in chronic lung injury and inhibits surfactant metabolism

2000 ◽  
Vol 278 (2) ◽  
pp. L382-L392 ◽  
Author(s):  
Jeevalatha Vivekananda ◽  
Vibhudutta Awasthi ◽  
Shanjana Awasthi ◽  
Dolphin B. Smith ◽  
Richard J. King
Keyword(s):  
Growth Factor ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Pulmonary Surfactant ◽  
Distress Syndrome ◽  
Lung Fibroblasts ◽  
Type Ii Cells ◽  
Type Ii ◽  
Hepatocyte Growth

Adult respiratory distress syndrome may incorporate in its pathogenesis the hyperplastic proliferation of alveolar epithelial type II cells and derangement in synthesis of pulmonary surfactant. Previous studies have demonstrated that hepatocyte growth factor (HGF) in the presence of serum is a potential mitogen for adult type II cells (R. J. Panos, J. S. Rubin, S. A. Aaronson, and R. J. Mason. J. Clin. Invest. 92: 969–977, 1993) and that it is produced by fetal mesenchymal lung cells (J. S. Rubin, A. M.-L. Chan, D. P. Botarro, W. H. Burgess, W. G. Taylor, A. C. Cech, D. W. Hirschfield, J. Wong, T. Miki, P. W. Finch, and S. A. Aaronson. Proc. Natl. Acad. Sci. USA 88: 415–419, 1991). In these studies, we expand on this possible involvement of HGF in chronic lung injury by showing the following. First, normal adult lung fibroblasts transcribe only small amounts of HGF mRNA, but the steady-state levels of this message rise substantially in lung fibroblasts obtained from animals exposed to oxidative stress. Second, inflammatory cytokines produced early in the injury stimulate the transcription of HGF in isolated fibroblasts, providing a plausible mechanism for the increased amounts of HGF seen in vivo. Third, HGF is capable of significantly inhibiting the synthesis and secretion of the phosphatidylcholines of pulmonary surfactant. Fourth, HGF inhibits the rate-limiting enzyme in de novo phosphatidylcholine synthesis, CTP:choline-phosphate cytidylyltransferase (EC 2.7.7.15 ). Our data indicate that fibroblast-derived HGF could be partially responsible for the changes in surfactant dysfunction seen in adult respiratory distress syndrome, including the decreases seen in surfactant phosphatidylcholines.

Parathyroid hormone-related protein-(38–64) regulates lung cell proliferation after silica injury

2002 ◽  
Vol 283 (1) ◽  
pp. L12-L21 ◽  
Author(s):  
Randolph H. Hastings ◽  
Angela Asirvatham ◽  
Rick Quintana ◽  
Rebeca Sandoval ◽  
Ruchika Dutta ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Parathyroid Hormone ◽  
Lung Injury ◽  
Nuclear Antigen ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Type Ii Cell

Inhalation of silica leads to acute lung injury and alveolar type II cell proliferation. Type II cell proliferation after hyperoxic lung injury is regulated, in part, by parathyroid hormone-related protein (PTHrP). In this study, we investigated lung PTHrP and its effects on epithelial proliferation after injury induced by silica. Lung PTHrP decreased modestly 4 days after we instilled 10 mg of silica into rat lungs and then recovered from 4 to 28 days. The number of proliferating cell nuclear antigen (PCNA)-positive type II cells was increased threefold in silica-injured lungs compared with controls. Subsequently, rats were treated with four exogenous PTHrP peptides in the silica instillate, which were administered subcutaneously daily. One peptide, PTHrP-(38–64), had consistent and significant effects on cell proliferation. PTHrP-(38–64) increased the median number of PCNA-positive cells/field nearly fourfold above controls, 380 vs. 109 ( P < 0.05). Thymidine incorporation was 2.5 times higher in type II cells isolated from rats treated with PTHrP-(38–64) compared with PBS. PTHrP-(38–64) significantly increased the number of cells expressing alkaline phosphatase, a type II cell marker. This study indicates that PTHrP-(38–64) stimulates type II cell growth and may have a role in lung repair in silica-injured rats.

Control of pulmonary surfactant secretion: an evolutionary perspective

2000 ◽  
Vol 278 (3) ◽  
pp. R611-R619 ◽  
Author(s):  
Philip G. Wood ◽  
Olga V. Lopatko ◽  
Sandra Orgeig ◽  
Jean M. P. Joss ◽  
Allan W. Smits ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Cultures ◽  
Pulmonary Surfactant ◽  
Parasympathetic Nervous System ◽  
Type Ii Cells ◽  
Type Ii ◽  
Surfactant System ◽  
Surfactant Secretion ◽  
Type Ii Cell ◽  
Australian Lungfish

Pulmonary surfactant, a mixture consisting of phospholipids (PL) and proteins, is secreted by type II cells in the lungs of all air-breathing vertebrates. Virtually nothing is known about the factors that control the secretion of pulmonary surfactant in nonmammalian vertebrates. With the use of type II cell cultures from Australian lungfish, North American bullfrogs, and fat-tailed dunnarts, we describe the autonomic regulation of surfactant secretion among the vertebrates. ACh, but not epinephrine (Epi), stimulated total PL and disaturated PL (DSP) secretion from type II cells isolated from Australian lungfish. Both Epi and ACh stimulated PL and DSP secretion from type II cells of bullfrogs and fat-tailed dunnarts. Neither Epi nor ACh affected the secretion of cholesterol from type II cell cultures of bullfrogs or dunnarts. Pulmonary surfactant secretion may be predominantly controlled by the autonomic nervous system in nonmammalian vertebrates. The parasympathetic nervous system may predominate at lower body temperatures, stimulating surfactant secretion without elevating metabolic rate. Adrenergic influences on the surfactant system may have developed subsequent to the radiation of the tetrapods. Furthermore, ventilatory influences on the surfactant system may have arisen at the time of the evolution of the mammalian bronchoalveolar lung. Further studies using other carefully chosen species from each of the vertebrate groups are required to confirm this hypothesis.

scholarly journals Chronic lung injury and impaired pulmonary function in a mouse model of acid ceramidase deficiency

2018 ◽  
Vol 314 (3) ◽  
pp. L406-L420 ◽  
Author(s):  
Fabian P. S. Yu ◽  
Diana Islam ◽  
Jakub Sikora ◽  
Shaalee Dworski ◽  
Jiří Gurka ◽  
...  
Keyword(s):  
Lung Function ◽  
Lung Injury ◽  
Mouse Model ◽  
Vascular Permeability ◽  
Phospholipid Composition ◽  
Blood Oxygenation ◽  
Lung Mechanics ◽  
Neurological Involvement ◽  
Lysosomal Storage ◽  
Acid Ceramidase

Farber disease (FD) is a debilitating lysosomal storage disorder (LSD) caused by a deficiency of acid ceramidase (ACDase) activity due to mutations in the gene ASAH1. Patients with ACDase deficiency may develop a spectrum of clinical phenotypes. Severe cases of FD are frequently associated with neurological involvement, failure to thrive, and respiratory complications. Mice homozygous ( Asah1P361R/P361R) for an orthologous patient mutation in Asah1 recapitulate human FD. In this study, we show significant impairment in lung function, including low compliance and increased airway resistance in a mouse model of ACDase deficiency. Impaired lung mechanics in Farber mice resulted in decreased blood oxygenation and increased red blood cell production. Inflammatory cells were recruited to both perivascular and peribronchial areas of the lung. We observed large vacuolated foamy histiocytes that were full of storage material. An increase in vascular permeability led to protein leakage, edema, and impacted surfactant homeostasis in the lungs of Asah1P361R/P361R mice. Bronchial alveolar lavage fluid (BALF) extraction and analysis revealed accumulation of a highly turbid lipoprotein-like substance that was composed in part of surfactants, phospholipids, and ceramides. The phospholipid composition of BALF from Asah1P361R/P361R mice was severely altered, with an increase in both phosphatidylethanolamine (PE) and sphingomyelin (SM). Ceramides were also found at significantly higher levels in both BALF and lung tissue from Asah1P361R/P361R mice when compared with levels from wild-type animals. We demonstrate that a deficiency in ACDase leads to sphingolipid and phospholipid imbalance, chronic lung injury caused by significant inflammation, and increased vascular permeability, leading to impaired lung function.

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