Autoradiographic Localization and Effects of Exogenous Radioactively Labelled Surfactant in the Lung of the Prematurely Delivered Fetal Rabbit

Winter, Isabel; Je, Scott; Mr, Oulton; Stinson, Dora A.; Allen, Alexander C.

doi:10.1159/000243420

Cited by 3 publications

(3 citation statements)

References 13 publications

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“…5 predicts that 80-100% of the bolus would deposit in the airways. In support of this prediction, Winter et al (44) reported that up to 80% of the surfactant given to fetal rabbits deposited in the conducting airways, speculating that the bolus volume was a factor contributing to the lack of alveolar deposition. Others have stated that 80-90% of a surfactant bolus reaches the alveoli (16).…”

Section: Phase 1: Bolus Dispersalmentioning

confidence: 95%

Bolus dispersal through the lungs in surfactant replacement therapy

Espinosa

Kamm

1999

Journal of Applied Physiology

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A model is presented of surfactant replacement therapy. An instilled bolus is pushed into the lungs on the first inspiration, coating the airways with a layer of surfactant and depositing some in the alveoli. Layer thickness depends on the capillary number (muU/gamma, where mu, U, and gamma are bolus viscosity, advancing meniscus velocity, and surface tension, respectively). Larger capillary number leads to thicker layers, reducing alveolar delivery. Subsequently, surface tension gradients sweep surfactant into alveoli not receiving surfactant during the first inspiration. The effects on spreading of sorption kinetics, bolus viscosity, initial layer thickness, initial penetration of surfactant, gravity, and shear stress are examined. Sorption nearly eliminates surface tension gradients in central airways but produces a sharp transition at the leading edge of the exogenous layer. Local thinning of the liquid layer results, trapping 95% of the surfactant in the airways. Gravity and ventilation augment transport somewhat. Transport to the periphery takes 4-170 s for the leading edge but considerably longer for the bulk of the surfactant. The model demonstrates how the various physical parameters governing surfactant distribution might alter the response to surfactant replacement therapy.

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Section: Phase 1: Bolus Dispersalmentioning

confidence: 95%

Bolus dispersal through the lungs in surfactant replacement therapy

Espinosa

Kamm

1999

Journal of Applied Physiology

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“…Binding was determined by measuring the to- tal counts of each section and dividing this by the area of that section to give mean counts per arbitrary unit area. The former samples were exposed for 4 wk, removed, fixed, developed, and stained as described previously (18). Control sections consisted of samples incubated with [ 125 I]leptin in the presence of 1 M-unlabeled leptin.…”

Section: Ligand-binding Assaysmentioning

confidence: 99%

Identification of Leptin Receptors in Lung and Isolated Fetal Type II Cells

Bergen

Cherlet

Manuel

et al. 2002

Am J Respir Cell Mol Biol

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Leptin is a cytokine involved in regulation of the satiety response. Receptors for this protein have been identified in brain as well as many other peripheral tissues. Some of the highest levels of receptor concentration occur in the lung. Considering the cellular diversity of lung, neither the localization nor the function of leptin in pulmonary tissues has been delineated. The purpose of the present study was to determine if fetal and adult rabbit lung displayed specific binding for leptin, to identify the binding sites, and to explore a potential functional role for leptin in lung surfactant production. Frozen sections of adult and fetal rabbit (24th gestational day) lung were prepared and incubated with increasing concentrations of [125I]leptin in the presence or absence of 1-microM-unlabeled leptin. Sections were removed and radioactivity measured. Concurrently, sections were coated with nuclear Trac emulsion and incubated in the dark at -30 degrees C. Lung showed specific binding for leptin. Microscopically, [125I]leptin was localized to acinar-lining epithelium of developing fetal lung. Larger cells within the epithelial layer appeared to bind leptin more avidly than adjacent cells. Antibodies to the leptin receptor were used to identify binding sites in adult lung and isolated fetal lung type II cells. In adult lung, both the K20 (against the extracellular amino-terminal) and the M18 antibody (against the intracellular carboxy-terminal) displayed several binding sites. In contrast, the isolated fetal type II cells showed only a single binding site for both antibodies. The apparent molecular mass of the receptor using the K20 antibody appeared to be approximately 125 kD. A protein of similar mass bound the M18 antibody suggesting that functional receptor is present in lung and expressed by fetal type II cells. Incubation of isolated fetal type II cells with leptin (0.01-10 microg/ml) stimulated [3H]choline incorporation in disaturated phosphatidylcholine. These results show that fetal and adult lung bind leptin specifically, and fetal type II cells in particular, may be responsive to leptin stimulation of phospholipid production. Leptin may therefore be important in regulating maturation of cells of the fetal lung.

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“…This indicates that ARS does not become tissue associated immediately after instillation but that it may be taken up by lung tissue during the first 60 min. In a previous study using radiolabeled ARS, we reported ϳ50% tissue association after 30 min of ventilation of 27-day gestation pups (36). It is possible that the tissue association occurs by rapid conversion to L, as observed in vitro (23), and immediate uptake of the L form by the type II cell.…”

Section: Discussionmentioning

confidence: 77%

Alveolar metabolism of natural vs. synthetic surfactants in preterm newborn rabbits

Allen¹,

Oulton²,

Stinson

et al. 2001

Journal of Applied Physiology

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We compared the recoveries of four surfactant preparations: two natural [term fetal rabbit surfactant (FRS) and adult rabbit surfactant (ARS)] and two commercially available preparations [apoprotein-based Survanta (S) and synthetic Exosurf (E)] from 27-day gestation rabbit pups treated at birth and ventilated up to 120 min. At 5, 60, and 120 min, we measured the recovery of the heavy-aggregate, metabolically active form (H) and the light-aggregate, nonsurface active metabolic breakdown form (L) of alveolar surfactant and determined the phospholipid content and composition of the intracellularly stored lamellar body (LB) pool. Pups treated with FRS had <15% loss of H by 2 h. ARS-treated pups had a >50% loss of H by 1 h, and E- and S-treated pups had approximately 50% loss by 5 min, with a slower rate of continuing loss of up to 80% by 2 h. The major losses of H phospholipid were not explained by the L-form recovery. LB phospholipid significantly increased only in the E-treated pups and only at 2 h. FRS provides a biologically active form (H) of surfactant that appeared to remain in the airway for a significantly longer time than the other surfactant preparations. The unique properties of FRS merit further study.

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Autoradiographic Localization and Effects of Exogenous Radioactively Labelled Surfactant in the Lung of the Prematurely Delivered Fetal Rabbit

Cited by 3 publications

References 13 publications

Bolus dispersal through the lungs in surfactant replacement therapy

Bolus dispersal through the lungs in surfactant replacement therapy

Identification of Leptin Receptors in Lung and Isolated Fetal Type II Cells

Alveolar metabolism of natural vs. synthetic surfactants in preterm newborn rabbits

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