Pulmonary oedema fluid induces non-alpha-ENaC-dependent Na+ transport and fluid absorption in the distal lung

Rafii, Bijan; Gillie, Daniel J.; Sulowski, Christopher; Hannam, Vicky; Cheung, Tony; Otulakowski, Gail; Barker, Pierre; O’Brodovich, Hugh

doi:10.1111/j..2002.t01-2-00537.x

Cited by 11 publications

(22 citation statements)

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“…Primary cultures of FDLE and their adjacent fibroblasts were obtained from 20-d timed gestation rat fetuses by enzymatic digestion, centrifugation, and differential adherence as previously described (19). ATII cells were isolated from 100 -200 g male Sprague Dawley rats by enzymatic digestion and purified based on differential adherence of cells to dishes coated with rat IgG (20).…”

Section: Methodsmentioning

confidence: 99%

Glucocorticoid-Mediated Repression of REDD1 mRNA Expression in Rat Fetal Distal Lung Epithelial Cells

et al. 2009

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REDD1 (Regulated in Development and DNA Damage-1) is a stress-response gene that represses mammalian target of rapamycin (mTOR) thus decreasing protein synthesis. In contrast to studies using cell lines and adult alveolar type II (ATII) cells, we find that REDD1 mRNA levels did not increase in rat fetal distal lung epithelia (FDLE) or fetal lung fibroblasts grown in primary cultures and then exposed to 3% O 2 . REDD1 mRNA expression was repressed by dexamethasone (DEX) in FDLE and ATII, but induced by DEX in fibroblasts. Lung epithelial cell lines, A549 and MLE-15, showed increases in REDD1 mRNA in response to hypoxia and DEX. The effect of DEX on REDD1 mRNA and protein in FDLE and fibroblasts was dose-and time-dependent. Inhibitor studies support repression of REDD1 mRNA by DEX in FDLE was mediated via glucocorticoid receptor and not by nongenomic effects of glucocorticoids via MAPK pathways. The half-life of REDD1 mRNA was shorter in DEX-exposed FDLE compared with hormone-free media suggesting that DEX reduced REDD1 mRNA stability in FDLE. These studies indicate that REDD1 expression in response to hypoxia and DEX is cell-type specific and that physiologically appropriate levels of PO 2 should be used when investigating fetal lung development. (Pediatr Res 65: 514-519, 2009) G lucocorticoid (GC) hormones are catabolic and affect both protein synthesis and degradation in many mammalian tissues, particularly in lymphoid tissues and skeletal muscle (1). In the lung, dexamethasone (DEX) has been shown to decrease protein synthetic rates by attenuating mRNA translation at two levels: translational efficiency (i.e. translation initiation) and translational capacity (i.e. ribosome biogenesis) (2). Because GC are used extensively to promote fetal lung maturation in women in preterm labor (3) and to treat a variety of acute and chronic lung conditions such as asthma, chronic obstructive pulmonary disease (4), and respiratory distress syndrome (5), it is essential that we develop an improved understanding of how individual lung cell types respond to GC exposure.GC exposure attenuates mRNA translation by a variety of signal transduction mechanisms (6), including decreased phosphorylation of the ribosomal protein S6 kinase (p70S6 K) and of the eukaryotic initiation factor (eIF)-4E-binding protein (4E-BP) (7). The serine-threonine kinase, mammalian target of rapamycin (mTOR) is a central integrator of environmental signals, including nutrients, growth factors, hormones, and hypoxia, and mTOR promotes mRNA translation by phosphorylating p70S6 K and 4E-BP (8). Recent publications have provided evidence that the protein encoded by REDD1 (Regulated in Development and DNA damage responses) may play a critical role in linking a variety of cues, including hypoxia and GC treatment, to inhibition of translation via the mTOR pathway (9 -11). DEXmediated induction of REDD1 transcription has been demonstrated in lymphoid cells (12) and in skeletal muscle in vivo and L6 myoblasts (10). In contrast, numerous publications have ...

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Section: Methodsmentioning

confidence: 99%

Glucocorticoid-Mediated Repression of REDD1 mRNA Expression in Rat Fetal Distal Lung Epithelial Cells

et al. 2009

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“…Distal lung epithelia (DLE) were isolated and grown in primary culture as described previously [15,16] from 20-day-gestation Wistar rats (Charles River; breeding day = day 0, term = 22 days). DLE were then seeded at a density of 1 × 10 6 cells/cm 2 onto 0.4-µm pore size Snapwell cell culture inserts (Corning Costar, Cambridge, MA, USA) for Ussing chamber studies, and 0.5 × 10 6 cells/cm 2 onto 12-well, 0.4-µm pore size Transwell cell culture inserts (Corning Costar) for ohmmeter, dextran flux, and sucrose flux studies.…”

Section: Cell Culturementioning

confidence: 99%

PROTEASE-ACTIVATED RECEPTOR (PAR)₁ALTERS BIOELECTRIC PROPERTIES OF DISTAL LUNG EPITHELIA WITHOUT COMPROMISING BARRIER FUNCTION

Moraes

Rafii

Niessen

et al. 2009

Experimental Lung Research

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Proteinases contribute to the pathogenesis of various lung diseases, partly through activating cell surface receptors by limited proteolytic cleavage. The authors provide evidence that in primary cultures of distal lung epithelia, basolateral protease-activated receptor 1 activation rapidly reduces transepithelial resistance but does not alter paracellular permeability to small uncharged solutes. Changes in transepithelial resistance were partially blocked by ion transport inhibitors and were completely blocked by placing cells in low chloride buffer. In vivo studies did not reveal enhanced lung permeability in response to pulmonary or intravenous administration of protease-activated receptor 1 activators. This information is relevant as strategies to inhibit protease-activated receptor 1 signaling are considered in order to preserve lung epithelial barrier function.

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“…The model of increased Pmv resulting in increased fluid influx balanced by increased fluid clearance does not hold in models of acute heart failure, or acute rise in Pmv, where alveolar fluid clearance has been found to decrease and pulmonary oedema manifest [13,[16][17][18]. Therefore, we may assume that in the presence of chronically elevated Pmv the pulmonary system is intrinsically changed in a manner which facilitates an increase in alveolar fluid clearance in parallel with increased fluid input, but that this can be overwhelmed, possibly by a sudden Pmv increase, or which may be less effective in a cohort of patients.…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Lung fluid clearance in chronic heart failure patients

Dixon

Pasquale

Lawrence

et al. 2017

International Journal of Cardiology

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Chronic elevation of pulmonary microvascular pressure (Pmv) consistently leads to alveolocapillary barrier thickening and reduction in the filtration coefficient. In animal models of chronic heart failure (CHF) the lung remains dry despite hydrostatic forces. As fluid flux is bi-directional, it has been postulated that an increase in alveolar fluid clearance may facilitate the dry lung when Pmv is chronically elevated. In this study we aimed to examine alveolar fluid clearance in ambulatory patients with CHF secondary to left ventricular (LV) systolic dysfunction compared against non-CHF controls. Lung clearance following aerosol delivery of 99m technetium (Tc)-diethyl triaminepentaacetic acid (DTPA) was measured non-invasively by scintigraphy and half time of 99m Tc-DTPA clearance (T (1/2)) was calculated by mono-exponential curve fit. Alveolar fluid clearance measured as half time DTPA clearance was significantly faster in CHF patients than controls (P = 0.001). This was further defined by NYHA classification. No correlation was found between DTPA clearance and plasma epinephrine, norepinephrine or aldosterone hormone (P > 0.05). Our results support an association between increasing alveolar fluid clearance and disease severity in CHF, and the concept of controlled bidirectional fluid flux in CHF associated with increasing Pmv, and represents another defence mechanism of the lung against pulmonary oedema.

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Pulmonary oedema fluid induces non-alpha-ENaC-dependent Na+ transport and fluid absorption in the distal lung

Cited by 11 publications

References 0 publications

Glucocorticoid-Mediated Repression of REDD1 mRNA Expression in Rat Fetal Distal Lung Epithelial Cells

Glucocorticoid-Mediated Repression of REDD1 mRNA Expression in Rat Fetal Distal Lung Epithelial Cells

PROTEASE-ACTIVATED RECEPTOR (PAR)₁ALTERS BIOELECTRIC PROPERTIES OF DISTAL LUNG EPITHELIA WITHOUT COMPROMISING BARRIER FUNCTION

Lung fluid clearance in chronic heart failure patients

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Pulmonary oedema fluid induces non-alpha-ENaC-dependent Na+ transport and fluid absorption in the distal lung

Cited by 11 publications

References 0 publications

Glucocorticoid-Mediated Repression of REDD1 mRNA Expression in Rat Fetal Distal Lung Epithelial Cells

Glucocorticoid-Mediated Repression of REDD1 mRNA Expression in Rat Fetal Distal Lung Epithelial Cells

PROTEASE-ACTIVATED RECEPTOR (PAR)1ALTERS BIOELECTRIC PROPERTIES OF DISTAL LUNG EPITHELIA WITHOUT COMPROMISING BARRIER FUNCTION

Lung fluid clearance in chronic heart failure patients

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PROTEASE-ACTIVATED RECEPTOR (PAR)₁ALTERS BIOELECTRIC PROPERTIES OF DISTAL LUNG EPITHELIA WITHOUT COMPROMISING BARRIER FUNCTION