Parathyroid hormone-related protein, an autocrine regulatory factor in alveolar epithelial cells

1996 ◽  
Vol 270 (3) ◽  
pp. L353-L361 ◽  
Author(s):  
R. H. Hastings ◽  
D. Summers-Torres ◽  
T. C. Cheung ◽  
L. S. Ditmer ◽  
E. M. Petrin ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Primary Cultures ◽  
A549 Cells ◽  
Alveolar Epithelial Cells ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Epithelial ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Receptor

Alveolar epithelial cells in vivo, primary cultures of adult rat type II cells, and human A549 alveolar carcinoma cells express parathyroid hormone-related protein (PTHrP). Here we demonstrated that type II cells and A549 cells also express the PTHrP receptor and that they exhibit differentiation-related responses to the amino-terminal PTHrP fragment, PTHrP-(1-34). PTHrP receptor expression in A549 cells was shown by detection of a 0.3-kb reverse transcriptase polymerase chain reaction product formed by primers specific for PTHrP receptor. In situ hybridization studies localized the site of production of PTHrP and PTHrP receptor mRNA in rat lung cells with morphology and location typical of type II cells. Primary cultures of such type II cells also expressed PTHrP receptor mRNA. Incubation with PTHrP-(1-34) stimulated disaturated phosphatidylcholine (DSPC) synthesis in A549 cells and increased the release of newly synthesized DSPC by cultured type II cells and A549 cells. In addition, PTHrP-(1-34) increased the number of lamellar bodies per type II cell and increased their expression of alkaline phosphatase in a dose-dependent manner. Thus PTHrP-(1-34) promoted a differentiated type II cell phenotype. Since cultured type II cells, alveolar epithelial cells in vivo, and A549 cells express PTHrP and the PTHrP receptor, PTHrP-(1-34) may be an autocrine regulatory factor in type II cells and lung cancer cells.

Hypoxia decreases proteins involved in epithelial electrolyte transport in A549 cells and rat lung

2000 ◽  
Vol 279 (6) ◽  
pp. L1110-L1119 ◽  
Author(s):  
Ralf Wodopia ◽  
Hyun Soo Ko ◽  
Javiera Billian ◽  
Rudolf Wiesner ◽  
Peter Bärtsch ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lung Tissue ◽  
A549 Cells ◽  
Alveolar Epithelial Cells ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
Alveolar Epithelial

Fluid reabsorption from alveolar space is driven by active Na reabsorption via epithelial Na channels (ENaCs) and Na-K-ATPase. Both are inhibited by hypoxia. Here we tested whether hypoxia decreases Na transport by decreasing the number of copies of transporters in alveolar epithelial cells and in lungs of hypoxic rats. Membrane fractions were prepared from A549 cells exposed to hypoxia (3% O2) as well as from whole lung tissue and alveolar type II cells from rats exposed to hypoxia. Transport proteins were measured by Western blot analysis. In A549 cells, α1- and β1-Na-K-ATPase, Na/K/2Cl cotransport, and ENaC proteins decreased during hypoxia. In whole lung tissue, α1-Na-K-ATPase and Na/K/2Cl cotransport decreased. α- and β-ENaC mRNAs also decreased in hypoxic lungs. Similar results were seen in alveolar type II cells from hypoxic rats. These results indicate a slow decrease in the amount of Na-transporting proteins in alveolar epithelial cells during exposure to hypoxia that also occurs in vivo in lungs from hypoxic animals. The reduced number of transporters might account for the decreased transport activity and impaired edema clearance in hypoxic lungs.

Dome formation in primary cultured monolayers of alveolar epithelial cells

1982 ◽  
Vol 243 (1) ◽  
pp. C96-C100 ◽  
Author(s):  
B. E. Goodman ◽  
E. D. Crandall
Keyword(s):  
Epithelial Cells ◽  
Life Span ◽  
Fluid Balance ◽  
Alveolar Epithelial Cells ◽  
Type Ii ◽  
Transport Function ◽  
Dome Formation ◽  
Alveolar Epithelial ◽  
Free Air

We have observed the formation of domes by type II alveolar epithelial cells harvested from rat lungs. The cells were harvested using elastase and grew to confluence in 3-4 days after plating on plastic. Numerous domes were observed in the monolayers 4-18 days after plating, with peak dome density occurring at days 6-9. When trypsin was used instead of elastase as the harvesting enzyme, many fewer domes were formed by the monolayers, with peak dome density observed at day 5 and no domes seen after 8 days. The life span of an individual dome was about 3-4 h. The presence of domes indicates an intact active transport function of the cells in the monolayer, which may represent an important mechanism for the maintenance of fluid-free air spaces and normal alveolar fluid balance in mammalian lungs in vivo.

Disparate cytokine regulation of ICAM-1 in rat alveolar epithelial cells and pulmonary endothelial cells in vitro

1995 ◽  
Vol 269 (1) ◽  
pp. L127-L135 ◽  
Author(s):  
W. W. Barton ◽  
S. Wilcoxen ◽  
P. J. Christensen ◽  
R. Paine
Keyword(s):  
Endothelial Cells ◽  
Epithelial Cells ◽  
Inflammatory Cytokines ◽  
Alveolar Epithelial Cells ◽  
Normal Lung ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Epithelial

Intercellular adhesion molecule-1 (ICAM-1) is expressed at high levels on type I alveolar epithelial cells in the normal lung and is induced in vitro as type II cells spread in primary culture. In contrast, in most nonhematopoetic cells ICAM-1 expression is induced in response to inflammatory cytokines. We have formed the hypothesis that the signals that control ICAM-1 expression in alveolar epithelial cells are fundamentally different from those controlling expression in most other cells. To test this hypothesis, we have investigated the influence of inflammatory cytokines on ICAM-1 expression in isolated type II cells that have spread in culture and compared this response to that of rat pulmonary artery endothelial cells (RPAEC). ICAM-1 protein, determined both by a cell-based enzyme-linked immunosorbent assay and by Western blot analysis, and mRNA were minimally expressed in unstimulated RPAEC but were significantly induced in a time- and dose-dependent manner by treatment with tumor necrosis factor-alpha, interleukin-1 beta, or interferon-gamma. In contrast, these cytokines did not influence the constitutive high level ICAM-1 protein expression in alveolar epithelial cells and only minimally affected steady-state mRNA levels. ICAM-1 mRNA half-life, measured in the presence of actinomycin D, was relatively long at 7 h in alveolar epithelial cells and 4 h in RPAEC. The striking lack of response of ICAM-1 expression by alveolar epithelial cells to inflammatory cytokines is in contrast to virtually all other epithelial cells studied to date and supports the hypothesis that ICAM-1 expression by these cells is a function of cellular differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Abrogation of ER stress-induced apoptosis of alveolar epithelial cells by angiotensin 1–7

2013 ◽  
Vol 305 (1) ◽  
pp. L33-L41 ◽  
Author(s):  
Bruce D. Uhal ◽  
Hang Nguyen ◽  
MyTrang Dang ◽  
Indiwari Gopallawa ◽  
Jing Jiang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Er Stress ◽  
Cathepsin D ◽  
Primary Cultures ◽  
A549 Cells ◽  
Surfactant Protein ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Induced Apoptosis ◽  
Jnk Activation

Earlier work showed that apoptosis of alveolar epithelial cells (AECs) in response to endogenous or xenobiotic factors is regulated by autocrine generation of angiotensin (ANG) II and its counterregulatory peptide ANG1–7. Mutations in surfactant protein C (SP-C) induce endoplasmic reticulum (ER) stress and apoptosis in AECs and cause lung fibrosis. This study tested the hypothesis that ER stress-induced apoptosis of AECs might also be regulated by the autocrine ANGII/ANG1–7 system of AECs. ER stress was induced in A549 cells or primary cultures of human AECs with the proteasome inhibitor MG132 or the SP-C BRICHOS domain mutant G100S. ER stress activated the ANGII-generating enzyme cathepsin D and simultaneously decreased the ANGII-degrading enzyme ACE-2, which normally generates the antiapoptotic peptide ANG1–7. TAPI-2, an inhibitor of ADAM17/TACE, significantly reduced both the activation of cathepsin D and the loss of ACE-2. Apoptosis of AECs induced by ER stress was measured by assays of mitochondrial function, JNK activation, caspase activation, and nuclear fragmentation. Apoptosis induced by either MG132 or the SP-C BRICHOS mutant G100S was significantly inhibited by the ANG receptor blocker saralasin and was completely abrogated by ANG1–7. Inhibition by ANG1–7 was blocked by the specific mas antagonist A779. These data show that ER stress-induced apoptosis is mediated by the autocrine ANGII/ANG1–7 system in human AECs and demonstrate effective blockade of SP-C mutation-induced apoptosis by ANG1–7. They also suggest that therapeutic strategies aimed at administering ANG1–7 or stimulating ACE-2 may hold potential for the management of ER stress-induced fibrotic lung disorders.

Secretion of cytokines by rat alveolar epithelial cells: possible regulatory role for SP-A

1994 ◽  
Vol 266 (2) ◽  
pp. L148-L155 ◽  
Author(s):  
H. Blau ◽  
S. Riklis ◽  
V. Kravtsov ◽  
M. Kalina
Keyword(s):  
Epithelial Cells ◽  
Alveolar Epithelial Cells ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
Long Term Culture ◽  
Alveolar Epithelial ◽  
Gm Csf

Cultured alveolar type II cells and pulmonary epithelial (PE) cells in long-term culture were found to secrete colony-stimulating factors (CSF) into the medium in similar fashion to alveolar macrophages. CSF activity was determined by using the in vitro assay for myeloid progenitor cells [colony-forming units in culture (CFU-C)]. Both lipopolisaccharide (LPS) and interleukin-1 alpha (IL-1 alpha) were found to upregulate the secretion 6.5- to 8-fold from alveolar type II cells and macrophages. However, no stimulatory effect of these factors was observed in PE cells that release CSF into the medium constitutively, possibly due to the conditions of long-term culture. The CSF activity was partially neutralized (70% inhibition) by antibodies against murine granulocyte/macrophage (GM)-CSF and IL-3, thus indicating the presence of both GM-CSF and IL-3-like factors in the CSF. However, the presence of other cytokines in the CSF is highly probable. Surfactant-associated protein A (SP-A), which is known to play a central role in surfactant homeostasis and function, was also found to upregulate secretion of CSF (at concentrations of 0.1-5 micrograms/ml) from alveolar type II cells and macrophages. Control cells such as rat peritoneal macrophages, alveolar fibroblasts, and 3T3/NIH cell line could not be elicited by SP-A to release CSF. The results are discussed in relation to the possible participation of the alveolar epithelial cells in various intercellular signaling networks. Our studies suggest that alveolar type II cells and SP-A may play an important regulatory role in the modulation of immune and inflammatory effector cells within the alveolar space.

Impairment of cation transport in A549 cells and rat alveolar epithelial cells by hypoxia

1997 ◽  
Vol 273 (4) ◽  
pp. L797-L806 ◽  
Author(s):  
Heimo Mairbäurl ◽  
Ralf Wodopia ◽  
Sigrid Eckes ◽  
Susanne Schulz ◽  
Peter Bärtsch
Keyword(s):  
Epithelial Cells ◽  
A549 Cells ◽  
Alveolar Epithelium ◽  
Cell Types ◽  
Cation Transport ◽  
Alveolar Epithelial Cells ◽  
Alveolar Type ◽  
Water Reabsorption ◽  
Alveolar Epithelial

A reduced cation reabsorption across the alveolar epithelium decreases water reabsorption from the alveoli and could diminish clearing accumulated fluid. To test whether hypoxia restricts cation transport in alveolar epithelial cells, cation uptake was measured in rat lung alveolar type II pneumocytes (AII cells) in primary culture and in A549 cells exposed to normoxia and hypoxia. In AII and A549 cells, hypoxia caused a[Formula: see text]-dependent inhibition of the Na-K pump, of Na-K-2Cl cotransport, and of total and amiloride-sensitive22Na uptake. Nifedipine failed to prevent hypoxia-induced transport inhibition in both cell types. In A549 cells, the inhibition of the Na-K pump and Na-K-2Cl cotransport occurred within ∼30 min of hypoxia, was stable >20 h, and was reversed by 2 h of reoxygenation. There was also a reduction in cell membrane-associated Na-K-ATPase and a decrease in Na-K-2Cl cotransport flux after full activation with calyculin A, indicating a decreased transport capacity. [14C]serine incorporation into cell proteins was reduced in hypoxic A549 cells, but inhibition of protein synthesis with cycloheximide did not reduce ion transport. In AII and A549 cells, ATP levels decreased slightly, and ADP and the ATP-to-ADP ratio were unchanged after 4 h of hypoxia. In A549 cells, lactate, intracellular Na, and intracellular K were unchanged. These results indicate that hypoxia inhibits apical Na entry pathways and the basolateral Na-K pump in A549 cells and rat AII pneumocytes in culture, indicating a hypoxia-induced reduction of transepithelial Na transport and water reabsorption by alveolar epithelium. If similar changes occur in vivo, the impaired cation transport across alveolar epithelial cells might contribute to the formation of hypoxic pulmonary edema.

scholarly journals Lectin binding patterns to terminal sugars of rat lung alveolar epithelial cells.

1990 ◽  
Vol 38 (2) ◽  
pp. 233-244 ◽  
Author(s):  
D J Taatjes ◽  
L A Barcomb ◽  
K O Leslie ◽  
R B Low
Keyword(s):  
Epithelial Cells ◽  
Lectin Binding ◽  
Alveolar Epithelial Cells ◽  
Gold Complex ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Rat Lung ◽  
Alveolar Epithelial ◽  
I Cells

We used post-embedding cytochemical techniques to investigate the lectin binding profiles of rat lung alveolar epithelial cells. Sections from rat lung embedded in the hydrophilic resin Lowicryl K4M were incubated either directly with a lectin-gold complex or with an unlabeled lectin followed by a specific glycoprotein-gold complex. The binding patterns of the five lectins used could be divided into three categories according to their reactivity with alveolar epithelial cells: (a) the Limax flavus lectin and Ricinus communis I lectin bound to both type I and type II cell plasma membranes; (b) the Helix pomatia lectin and Sambucus nigra L. lectin bound to type II but not type I cells; and (c) the Erythrina cristagalli lectin reacted with type I cells but was unreactive with type II cells. The specificity of staining was assessed by control experiments, including pre-absorption of the lectins with various oligosaccharides and enzymatic pre-treatment of sections with highly purified glycosidases to remove specific sugar residues. The results demonstrate that these lectins can be used to distinguish between type I and type II cells and would therefore be useful probes for investigating cell dynamics during lung development and remodeling.

In vivo blockade of KCa3.1 ion channel alleviates ER stress in type II alveolar epithelial cells and macrophages in pulmonary fibrosis

2019 ◽  
Author(s):  
K. Udari Eshani Perera ◽  
Sasika Nimanthi Vithana Dewage ◽  
Habtamu B. Derseh ◽  
Paul John Benham ◽  
Andrew Stent ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Pulmonary Fibrosis ◽  
Ion Channel ◽  
Er Stress ◽  
Alveolar Epithelial Cells ◽  
Type Ii ◽  
Alveolar Epithelial

Injury of rat pulmonary alveolar epithelial cells by H2O2: dependence on phenotype and catalase

1991 ◽  
Vol 260 (4) ◽  
pp. L318-L325 ◽  
Author(s):  
R. H. Simon ◽  
J. A. Edwards ◽  
M. M. Reza ◽  
R. G. Kunkel
Keyword(s):  
Epithelial Cells ◽  
Catalase Activity ◽  
Lung Diseases ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Epithelial

In a variety of inflammatory lung diseases, type I alveolar epithelial cells are more likely to be injured than are type II cells. Because oxidants have been implicated as a cause of injury in various inflammatory lung diseases, we evaluated the effects of differentiation on alveolar epithelial cell susceptibility to H2O2-induced injury. With the use of isolated rat type II cells in culture, we found that the cytotoxic effect of H2O2 increased between days 2 and 7, when type II cells are known to lose their distinctive type II properties and assume a more type I-like appearance. We previously reported that type II cells utilized both intracellular catalase and glutathione-dependent reactions to protect against H2O2. We therefore examined whether alterations in either of these protective mechanisms were responsible for the differentiation-dependent changes in sensitivity to H2O2. We found that catalase activity within alveolar epithelial cells decreased between 2 and 7 days in culture, whereas no changes were detected in glutathione-dependent systems. We then used a histochemical technique that detects catalase activity and found that type II cells within rat lungs possessed numerous catalase-containing peroxisomes, whereas very few were detected in type I cells. These findings demonstrate that as type II cells assume a type I-like phenotype, they become more susceptible to H2O2-induced injury. This increased susceptibility is associated with reductions in intracellular catalase activity, both in vitro and in vivo.

In Vivo and in Vitro Expression of Metallothionein in Injured Type II Alveolar Epithelial Cells

CHEST Journal ◽  
1994 ◽  
Vol 105 (3) ◽  
pp. 78S
Author(s):  
Bruce Piedboeuf ◽  
William Maniscalco ◽  
Stephen Hall ◽  
Maura Campbell ◽  
Richard Watkins ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Alveolar Epithelial Cells ◽  
Type Ii ◽  
In Vitro Expression ◽  
Alveolar Epithelial
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