Composition of alveolar liquid in the foetal lamb

Adamson, T. M.; Boyd, Robert D.; Platt, H.; Strang, L. B.

doi:10.1113/jphysiol.1969.sp008905

Cited by 139 publications

(60 citation statements)

References 13 publications

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“…It is also conceivable that the chemical composition of fetal lung fluid may impair transduction of fetal airways. Unlike cell culture mediums, which are optimized to achieve efficient viral vector transduction in vitro, ovine fetal lung fluid is mildly acidic (pHB6.27), hyperchloremic (157 mEq l À1 ) and contains little bicarbonate (2.8 mEq l À1 ) 42 or oxygen. In contrast, low extracellular pH is required for fusion of the JSRV envelope to HYAL2 (ref.…”

Section: Discussionmentioning

confidence: 99%

Jaagsiekte sheep retrovirus pseudotyped lentiviral vector-mediated gene transfer to fetal ovine lung

et al. 2011

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Viral vector-mediated gene transfer to the postnatal respiratory epithelium has, in general, been of low efficiency due to physical and immunological barriers, non-apical location of cellular receptors critical for viral uptake and limited transduction of resident stem/progenitor cells. These obstacles may be overcome using a prenatal strategy. In this study, HIV-1-based lentiviral vectors (LVs) pseudotyped with the envelope glycoproteins of Jaagsiekte sheep retrovirus (JSRV-LV), baculovirus GP64 (GP64-LV), Ebola Zaire-LV or vesicular stomatitis virus (VSVg-LV) and the adeno-associated virus-2/6.2 (AAV2/6.2) were compared for in utero transfer of a green fluorescent protein (GFP) reporter gene to ovine lung epithelium between days 65 and 78 of gestation. GFP expression was examined on day 85 or 136 of gestation (term is B145 days). The percentage of the respiratory epithelial cells expressing GFP in fetal sheep that received the JSRV-LV (3.18Â10 8 -6.85Â10 9 viral particles per fetus) was 24.6 ± 0.9% at 3 weeks postinjection (day 85) and 29.9±4.8% at 10 weeks postinjection (day 136). Expression was limited to the surface epithelium lining fetal airways o100 mm internal diameter. Fetal airways were amenable to VSVg-LV transduction, although the percentage of epithelial expression was low (6.6 ± 0.6%) at 1 week postinjection. GP64-LV, Ebola Zaire-LV and AAV2/6.2 failed to transduce the fetal ovine lung under these conditions. These data demonstrate that prenatal lung gene transfer with LV engineered to target apical surface receptors can provide sustained and high levels of transgene expression and support the therapeutic potential of prenatal gene transfer for the treatment of congenital lung diseases.

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Section: Discussionmentioning

confidence: 99%

Jaagsiekte sheep retrovirus pseudotyped lentiviral vector-mediated gene transfer to fetal ovine lung

et al. 2011

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“…In the 1960s, Adams et al 2 showed that the fetal lung liquid usually has a high Cl À ion concentration and that movement of liquid into the developing fetal lung's lumen occurred as a result of the active transport of ions by the epithelium. 3,4 This fluid secretion, which distended the fetal lung and flowed out into the amniotic space, has been shown by clinical observations to have physiological significance. When the volume of fetal lung fluid is abnormally small, lung hypoplasia occurs, as in conditions such as oligohydramnios, 5 pulmonary arterial occlusion 6,7 and chronic drainage of fluid from the lungs of fetal sheep.…”

Section: Fetal Lung Fluid Secretionmentioning

confidence: 99%

“…12 The cellular mechanisms that are responsible for fetal lung fluid secretion are well described in Figure 1; fetal lung fluid secretion arises from active Cl À secretion by the fetal distal lung epithelia. 3,4,13 Regulation of fluid secretion via control of Cl À transport has been investigated in a few studies that showed upregulation of lung fluid secretion by prostaglandins, growth factors and decrease of alveolar space size. Interestingly, it was observed in a mouse model that Cl À -driven fluid secretion is independent of cystic fibrosis transmembrane regulator, which may explain the absence of defective lung growth in cystic fibrosis.…”

Section: Fetal Lung Fluid Secretionmentioning

confidence: 99%

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Clinical implication of lung fluid balance in the perinatal period

2011

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At birth, lung fluid produced during fetal life must be cleared immediately and efficiently before the first breath takes place, in order for infants to achieve a normal and successful transition from prenatal to postnatal life. Postnatal lung fluid resorption is mediated through activation of airway epithelial sodium channels (ENaC). The observation that ENaC expression is a gestational age-dependent process contributes to our understanding of the development of respiratory distress in both term and preterm infants due to impaired clearing of fluid from their lungs. As fluid absorption, mediated by ENaC activity, in postnatal life has a significant biological role in preventing respiratory distress, any strategy that enhances ENaC activity can potentially help to decrease its incidence and associated morbidity.

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“…All concentrations, measured per unit of volume, were expressed per kg H20, using values for the water concentration of plasma and lung liquid in Adamson et al (1969).…”

Section: Methodsmentioning

confidence: 99%

Ion fluxes across the pulmonary epithelium and the secretion of lung liquid in the foetal lamb

Olver¹,

Strang²

1974

The Journal of Physiology

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312

168

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2. The permeability sequence of the pulmonary epithelium for alkali metals was, Na+ > K+ > Rb+ > Li+ > Cs+ and that for halides I-Br-> C1-. Permeabilities to alkaline earths were lower than for the other ions, no definite sequence being established.3. There was an electrical potential difference of -1 to -10 mV (mean -4.3 mV) between lung liquid and plasma (lung liquid negative). Plasma/lung liquid chemical activity ratios were less than unity for the halides (Cl-, Br-, I-), and for K+ and Rb+, whereas the ratio of oneway fluxes (plasma --lung liquid)/(lung liquid -+ plasma) was in each case greater than unity. From the difference between the measured flux ratios and those predicted from the forces determining passive flux, it was concluded that the halides, K+ and Rb+ were actively transported from plasma to lung liquid, Cl-being quantitatively the most important. Na+ and Ca2+ appeared to move passively down a gradient of electrochemical potential.R. E. OLVER AND L. B. STRANG 4. When alveolar liquid [HCO ] was artificially raised, a net flux of HCO-from lung liquid against a gradient of electrochemical activity was observed, suggesting active transport of that ion out of lung liquid.5. The addition of KCN to lung liquid stopped the secretion of liquid and absorption took place.

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Composition of alveolar liquid in the foetal lamb

Cited by 139 publications

References 13 publications

Jaagsiekte sheep retrovirus pseudotyped lentiviral vector-mediated gene transfer to fetal ovine lung

Jaagsiekte sheep retrovirus pseudotyped lentiviral vector-mediated gene transfer to fetal ovine lung

Clinical implication of lung fluid balance in the perinatal period

Ion fluxes across the pulmonary epithelium and the secretion of lung liquid in the foetal lamb

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