Hypoxia reduces endothelin production by rat alveolar type II cells in primary culture

Crestani, Bruno; Odoux, Christine; Rolland, Corinne; Moldovan, Florina; Cornillet, Pascale; Fiet, Jean; Aubier, Michel

doi:10.1183/09031936.98.11020392

Cited by 7 publications

(6 citation statements)

References 39 publications

(53 reference statements)

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“…However, ET-1 secretion was suppressed by hypoxia and anoxia in pulmonary epithelial cells. This phenomenon has been reported previously for both A549 cells and primary rat alveolar type II cells [45]. Although animal studies indicate that ET-1 can exert profound effects on the function of alveolar epithelial cells, the mechanisms of ET-1 processing within alveolar epithelial cells are not known at this time.…”

Section: Discussionsupporting

confidence: 78%

Differential Effects of Hypoxic Stress in Alveolar Epithelial Cells and Microvascular Endothelial Cells

Signorelli

Jennings

Leonard

et al. 2010

Cell Physiol Biochem

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Under hypoxic conditions eukaryotic cells and tissues undergo adaptive responses involving glycolysis, angiogenesis, vasoconstriction and inflammation. The underlying molecular mechanisms are not yet fully elucidated and are most likely cell and tissue specific. In the lung, alveolar epithelial cells and microvascular endothelial cells are highly sensitive to hypoxia and together orchestrate a rapid and sustained adaptive response. We examined the effect of different oxygen tensions on cell viability, glucose metabolism, key transcription factors and signaling molecules, in alveolar epithelial cells (A549) and microvascular endothelial cells (HMEC-1). Both cell types tolerated hypoxia without detectable cell injury. Hypoxia induced glycolysis in both epithelial and microvascular endothelial cells, although A549 cells exhibited a higher rate of glucose consumption. The transcription factor CREB (cAMP response element binding protein) was activated with decreasing oxygen tensions in both cell types. This effect was again more marked in A549 cells, demonstrating epithelial cells to be more oxygen sensitive. Activating Transcription Factor 3 (ATF-3) was heavily induced by hypoxia in A549 cells but not in HMEC-1 cells. Both cell types exhibited hypoxia induced secretion of VEGF and IL-6. Secretion of the vasoconstrictor endothelin-1 (ET1) was increased by hypoxia in HMEC-1 cells but decreased in A549 cells. These data reveal that both cell types exhibit an adaptive response to hypoxia but alveolar epithelial cells are generally more sensitive. ET-1 was oppositely regulated by decreased oxygen tensions in the investigated cell types. The present study further elucidates the adaptive molecular mechanisms in pulmonary hypoxia and demonstrates cell specific responses.

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Section: Discussionsupporting

confidence: 78%

Differential Effects of Hypoxic Stress in Alveolar Epithelial Cells and Microvascular Endothelial Cells

Signorelli

Jennings

Leonard

et al. 2010

Cell Physiol Biochem

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“…In agreement with this possibility, there are some reports on the expression of ET in this cell type (Rozengurt et al, 1990;Giaid et al 1993;Crestani et al 1998). The secretion of surfactant by Type II pneumocytes has been reported to be stimulated by ET (Sen et al 1994).…”

Section: Discussionsupporting

confidence: 62%

Immunohistochemical Mapping of Endothelin in the Developing and Adult Mouse Lung

Guembe

Villaro

2001

J Histochem Cytochem.

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Endothelins (ET) are a family of regulatory peptides displaying, among other abilities, potent constrictor actions. We studied the perinatal time course expression and distribution of ET in the mouse airway epithelium. In fetal mouse, ET-immunoreactivity (IR) appeared earlier (gestational Day 18) in the epithelium of upper (bronchi and large bronchioles) than in lower airways, being scarce and mainly located in the apical cytoplasm. As the lung developed, ET-IR became gradually stronger and extended throughout the cell in both bronchi and bronchioles. ET-IR was found in most airway epithelial cells. Clara cells were positive for ET, whereas ciliated and endocrine cells were not. In adult lungs, part of the myocytes and parenchymal cells also showed ET-IR. In both developing and adult mouse lungs, the cell distribution of ET-IR in the epithelium is compatible with apical and/or basal secretion. The presence of ET in mouse airway epithelium during the perinatal period may indicate a role for ET as a growth factor in lung development and its involvement in control of lung ventilation at birth.

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“…However, an increased arterial ET-1 level in hypoxemic COPD patients seems to be in contrast with some recent experimental findings. Crestani et al [14]recently showed that hypoxemia reduces ET production of rat alveolar type II cells in primary culture. Jankov et al [15]demonstrated that in neonatal rats, hyperoxia caused increased ET-1 levels and PH.…”

Section: Discussionmentioning

confidence: 99%

Plasma and Bronchoalveolar Lavage Fluid Levels of Endothelin-1 in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension

Bacakoğlu

Atasever²,

Özhan³

et al. 2003

Respiration

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Background: Secondary pulmonary hypertension (PH) and cor pulmonale are the major clinical cardiovascular complications affecting prognosis in patients with chronic obstructive pulmonary disease (COPD). It is also known that endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by the pulmonary vascular endothelium, and ET-1 may be implicated in the pathogenesis of PH. Objectives: The purpose of this study was to investigate the presence of ET-1 in patients with COPD and to assess the correlation of ET-1 levels in the plasma and bronchoalveolar lavage (BAL) fluid (BALF) in COPD patients with or without PH. Methods: Twenty-two patients with COPD and 15 healthy controls were enrolled in the study. Peripheral venous blood samples were collected in all patients and controls. BAL was obtained in COPD patients, and ET-1 levels were measured by radioimmunoassay in all plasma and BALF samples. Results: Plasma ET-1 levels were 2.46 ± 0.55 and 1.70 ± 0.42 pmol/dl in patients with COPD and controls, respectively (p < 0.0001). Sixteen of the 22 patients with COPD (73%) had PH established by echocardiography. The ET-1 level in these patients amounted to 2.59 ± 0.50 pmol/dl, and it was 2.10 ± 0.54 pmol/dl in 6 patients with COPD without PH. In COPD patients with and without PH, BALF ET-1 levels were 0.19 ± 0.08 and 0.24 ± 0.01 pmol/dl, respectively (p > 0.05). Conclusions: These results suggest that ET-1 is detectable in both the peripheral blood and BALF of COPD patients, but the levels do not statistically differ between patients with and without PH.

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Hypoxia reduces endothelin production by rat alveolar type II cells in primary culture

Cited by 7 publications

References 39 publications

Differential Effects of Hypoxic Stress in Alveolar Epithelial Cells and Microvascular Endothelial Cells

Differential Effects of Hypoxic Stress in Alveolar Epithelial Cells and Microvascular Endothelial Cells

Immunohistochemical Mapping of Endothelin in the Developing and Adult Mouse Lung

Plasma and Bronchoalveolar Lavage Fluid Levels of Endothelin-1 in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension

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