scholarly journals Regulation of lung cell proliferation by polypeptide growth factors

1989 ◽  
Vol 257 (2) ◽  
pp. L23-L38 ◽  
Author(s):  
R. J. King ◽  
M. B. Jones ◽  
P. Minoo
Keyword(s):  
Growth Factors ◽  
Respiratory Failure ◽  
Epithelial Cells ◽  
Acute Respiratory Failure ◽  
Traumatic Injury ◽  
Alveolar Epithelial Cells ◽  
Metabolic Effects ◽  
Cell Populations ◽  
Type I ◽  
Polypeptide Growth Factors

In the last 10 years there has been an increased appreciation of the changes in lung cell populations that occur in association with the acute respiratory failure often induced by traumatic injury. Early events result in an accumulation in the lung of platelets, neutrophils, monocytes, and macrophages, a release of substances having potent cardiopulmonary and metabolic effects, and an ensuing edema and transudation of materials from the interstitium and capillaries into the alveoli. Further progression of the injury results in significant decreases in the number of endothelial and type I epithelial cells and a subsequent hyperplasia of fibroblasts and type II-like epithelial cells. Major sequelae of the latter stage of the disease are interstitial and interalveolar fibrosis, probably resulting from the increased number of fibroblasts present. The activity and composition of pulmonary surfactant are often perturbed. This review will discuss mechanisms that may be involved in these processes, with major emphasis on cell-cell interactions mediated through polypeptide growth factors. We describe the properties of certain growth factors commonly associated with inflammatory and wound healing reactions, discuss their cellular origins, and speculate on their possible roles in mediating the structural and physiological responses seen in the lung during acute respiratory failure. The majority of work done with lung cells has concentrated on interactions between macrophages and fibroblasts, and it is evident that macrophages are capable of producing mitogens affecting the proliferation of fibroblasts. However, from the results of studies that are less developed, it is possible that epithelial cells and immunologically stimulated cells could also be involved in these actions. We conclude that the homeostasis of lung cell populations may be influenced by both growth-stimulating and growth-inhibiting substances and potentially could involve interactions through growth factors of fibroblasts, macrophages, lymphocytes, alveolar epithelial cells, endothelial cells, and platelets. At this time the information on these purported interactions is quite limited and there are far more questions than answers.

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)

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.

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.

scholarly journals Radiation Induces Pulmonary Fibrosis by Promoting the Fibrogenic Differentiation of Alveolar Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Lu-Kai Wang ◽  
Tsai-Jung Wu ◽  
Ji-Hong Hong ◽  
Fang-Hsin Chen ◽  
John Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Tissue Growth ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Alveolar Cells ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Radiation Induced

The lung is a radiosensitive organ, which imposes limits on the therapeutic dose in thoracic radiotherapy. Irradiated alveolar epithelial cells promote radiation-related pneumonitis and fibrosis. However, the role of lung stem cells (LSCs) in the development of radiation-induced lung injury is still unclear. In this study, we found that both LSCs and LSC-derived type II alveolar epithelial cells (AECII) can repair radiation-induced DNA double-strand breaks, but the irradiated LSCs underwent growth arrest and cell differentiation faster than the irradiated AECII cells. Moreover, radiation drove LSCs to fibrosis as shown with the elevated levels of markers for epithelial-mesenchymal transition and myofibroblast (α-smooth muscle actin (α-SMA)) differentiation in in vitro and ex vivo studies. Increased gene expressions of connective tissue growth factor and α-SMA were found in both irradiated LSCs and alveolar cells, suggesting that radiation could induce the fibrogenic differentiation of LSCs. Irradiated LSCs showed an increase in the expression of surfactant protein C (SP-C), the AECII cell marker, and α-SMA, and irradiated AECII cells expressed SP-C and α-SMA. These results indicated that radiation induced LSCs to differentiate into myofibroblasts and AECII cells; then, AECII cells differentiated further into either myofibroblasts or type I alveolar epithelial cells (AECI). In conclusion, our results revealed that LSCs are sensitive to radiation-induced cell damage and may be involved in radiation-induced lung fibrosis.

scholarly journals Nanoparticle (NP) uptake by type I alveolar epithelial cells and their oxidant stress response

2009 ◽  
Vol 3 (4) ◽  
pp. 307-318 ◽  
Author(s):  
Beth A. VanWinkle ◽  
Karen L. De Mesy Bentley ◽  
Jonathan M. Malecki ◽  
Karlene K. Gunter ◽  
Irene M. Evans ◽  
...  
Keyword(s):  
Stress Response ◽  
Epithelial Cells ◽  
Oxidant Stress ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Alveolar Epithelial

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.

scholarly journals Modification of Type I Collagenous Gels by Alveolar Epithelial Cells

2000 ◽  
Vol 22 (6) ◽  
pp. 702-707 ◽  
Author(s):  
Takeshi Umino ◽  
Hangjun Wang ◽  
Yunkui Zhu ◽  
Xiangde Liu ◽  
Lidia S. Manouilova ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Alveolar Epithelial

scholarly journals Transient receptor vanilloid 4 (TRPV4) channels are essential for alveolar epithelial cell function

2019 ◽  
Author(s):  
Jonas Weber ◽  
Yu-Kai Chao ◽  
Martina Kannler ◽  
Gabriela Krasteva-Christ ◽  
Suhasini Rajan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Barrier Function ◽  
Alveolar Epithelial Cells ◽  
Transient Receptor Potential Vanilloid ◽  
Alveolar Type ◽  
Type I ◽  
Edema Formation ◽  
Genetic Ablation ◽  
Alveolar Epithelial ◽  
Transient Receptor

AbstractIschemia-reperfusion(IR)-induced edema formation can be mimicked ex-vivo in isolated perfused mouse lungs (IPL). Here we show enhanced edema formation in transient receptor potential vanilloid 4 (TRPV4)-deficient (TRPV4-/-) IPL compared to wild-type (WT) controls in response to IR, indicating a protective role of TRPV4 to maintain the alveolar epithelial barrier. By immunohistochemistry, mRNA profiling or electrophysiological analysis we detected TRPV4 in bronchial epithelium, alveolar type I (ATI) and alveolar type II (ATII) cells. Genetic ablation of TRPV4 resulted in reduced expression of aquaporin-5 (AQP-5) channels in ATI as well as decreased production of pro surfactant protein C (pSP-C) in ATII cells. Migration of TRPV4-deficient ATI cells was reduced and cell barrier function was impaired. Moreover, adult TRPV4−/− lungs developed emphysema-like changes and altered lung parameters compared to WT lungs. Therefore, our data highlight novel essential functions of TRPV4 channels in alveolar epithelial cells and in the protection from edema formation.eLife digestTransient receptor potential vanilloid 4 (TRPV4) is a non-selective Ca2+ permeable cation channel expressed in lung endothelium where increased channel activity has been shown to compromise endothelial barrier function. In other tissues however, the channel maintains physiological cell barriers, e.g. in skin, the urogenital tract and the corneal epithelium. In tracheal epithelial cells TRPV4 channels regulate ciliar beat frequency and in alveolar epithelial cells TRPV4 activation by 4α-phorbol esters produced blebs and breaks in lung septa by unknown molecular mechanisms. To understand the channels role in lung function Weber et al. employed ex-vivo isolated perfused mouse lungs (IPL) to mimic ischemia-reperfusion-induced edema as one of the most common and significant causes of morbidity and mortality after lung transplantation in human patients. TRPV4-deficient (TRPV4−/−) IPL developed enhanced edema formation compared to wild-type (WT) controls in response to ischemia and reperfusion, indicating a protective role of TRPV4 to maintain the alveolar epithelial barrier. TRPV4 was detected in bronchial epithelium, alveolar type I (ATI) and alveolar type II (ATII) cells by immunohistochemistry or mRNA profiling. Genetic ablation of TRPV4 resulted in reduced expression and plasma membrane insertion of water conducting aquaporin-5 (AQP-5) channels in ATI cells compared to WT mice. Analysis of isolated primary TRPV4−/− ATII cells revealed a reduced expression of pro surfactant protein-C (pSP-C) a precursor of a protein important for decreasing surface tension and for alveolar fluid homeostasis. Moreover, the TRPV4 activator GSK1016790A induced increases in current densities only in WT but not in TRPV4−/− ATII cells. On a molecular level ablation of TRPV4 induced less Ca2+-mediated nuclear translocation of nuclear factor of activated T-cells (NFAT) to the nucleus, which may be responsible for reduced expression of the identified proteins. Although the ability of TRPV4−/− ATII to differentiate to ATI cells was unchanged, migration of TRPV4-deficient ATI cells was reduced and cell barrier function was impaired. Moreover, TRPV4−/− lungs of adult mice developed significantly larger mean chord lengths and altered lung function compared to WT lungs. The findings of Weber et al. highlights novel essential functions of TRPV4 channels in alveolar epithelial cells and in the protection from edema formation.

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