scholarly journals Surfactant dysfunction during overexpression of TGF-β1 precedes profibrotic lung remodeling in vivo

2016 ◽  
Vol 310 (11) ◽  
pp. L1260-L1271 ◽  
Author(s):  
Elena Lopez-Rodriguez ◽  
Caroline Boden ◽  
Mercedes Echaide ◽  
Jesus Perez-Gil ◽  
Martin Kolb ◽  
...  

Transforming growth factor-β1 (TGF-β1) is involved in regulation of cellular proliferation, differentiation, and fibrogenesis, inducing myofibroblast migration and increasing extracellular matrix synthesis. Here, TGF-β1 effects on pulmonary structure and function were analyzed. Adenovirus-mediated gene transfer of TGF-β1 in mice lungs was performed and evaluated by design-based stereology, invasive pulmonary function testing, and detailed analyses of the surfactant system 1 and 2 wk after gene transfer. After 1 wk decreased static compliance was linked with a dramatic alveolar derecruitment without edema formation or increase in the volume of septal wall tissue or collagen fibrils. Abnormally high surface tension correlated with downregulation of surfactant proteins B and C. TTF-1 expression was reduced, and, using PLA (proximity ligand assay) technology, we found Smad3 and TTF-1 forming complexes in vivo, which are normally translocated into the nucleus of the alveolar epithelial type II cells (AE2C) but in the presence of TGF-β1 remain in the cytoplasm. AE2C show altered morphology, resulting in loss of total apical surface area per lung and polarity. These changes of AE2C were progressive 2 wk after gene transfer and correlated with lung compliance. Although static lung compliance remained low, the volume of septal wall tissue and collagen fibrils increased 2 wk after gene transfer. In this animal model, the primary effect of TGF-β1 signaling in the lung is downregulation of surfactant proteins, high surface tension, alveolar derecruitment, and mechanical stress, which precede fibrotic tissue remodeling and progressive loss of AE2C polarity. Initial TTF-1 dysfunction is potentially linked to downregulation of surfactant proteins.

1985 ◽  
Vol 58 (1) ◽  
pp. 129-136 ◽  
Author(s):  
G. F. Nieman ◽  
C. E. Bredenberg

The effect of the detergent dioctyl sodium sulfosuccinate on pulmonary extravascular water volume (PEWV) was studied in adult anesthetized mongrel dogs. The detergent was dissolved as a 1% solution in a vehicle of equal volumes of 95% ethanol and normal saline and administered by ultrasonic nebulizer attached to the inspiratory tubing of a piston ventilator. Two hours following detergent aerosol PEWV measured gravimetrically was increased compared with either animals receiving no aerosol or those receiving an aerosol of vehicle alone. Loss of surfactant activity and increased alveolar surface tension were demonstrated by Wilhelmy balance studies of minced lung extracts, by a fall in static compliance, and by evidence of atelectasis and instability noted by gross observation and by in vivo microscopy. No significant changes in colloid oncotic pressure or pulmonary microvascular hydrostatic pressure were observed. These data suggest that pulmonary edema can be induced by increased alveolar surface tension and support the concept that one of the major roles of pulmonary surfactant is to prevent pulmonary edema.


2019 ◽  
Vol 20 (17) ◽  
pp. 4243 ◽  
Author(s):  
Nina Rühl ◽  
Elena Lopez-Rodriguez ◽  
Karolin Albert ◽  
Bradford J Smith ◽  
Timothy E Weaver ◽  
...  

High surface tension at the alveolar air-liquid interface is a typical feature of acute and chronic lung injury. However, the manner in which high surface tension contributes to lung injury is not well understood. This study investigated the relationship between abnormal alveolar micromechanics, alveolar epithelial injury, intra-alveolar fluid properties and remodeling in the conditional surfactant protein B (SP-B) knockout mouse model. Measurements of pulmonary mechanics, broncho-alveolar lavage fluid (BAL), and design-based stereology were performed as a function of time of SP-B deficiency. After one day of SP-B deficiency the volume of alveolar fluid V(alvfluid,par) as well as BAL protein and albumin levels were normal while the surface area of injured alveolar epithelium S(AEinjure,sep) was significantly increased. Alveoli and alveolar surface area could be recruited by increasing the air inflation pressure. Quasi-static pressure-volume loops were characterized by an increased hysteresis while the inspiratory capacity was reduced. After 3 days, an increase in V(alvfluid,par) as well as BAL protein and albumin levels were linked with a failure of both alveolar recruitment and airway pressure-dependent redistribution of alveolar fluid. Over time, V(alvfluid,par) increased exponentially with S(AEinjure,sep). In conclusion, high surface tension induces alveolar epithelial injury prior to edema formation. After passing a threshold, epithelial injury results in vascular leakage and exponential accumulation of alveolar fluid critically hampering alveolar recruitability.


1998 ◽  
Vol 84 (1) ◽  
pp. 146-156 ◽  
Author(s):  
Olga V. Lopatko ◽  
Sandra Orgeig ◽  
Christopher B. Daniels ◽  
David Palmer

Lopatko, Olga V., Sandra Orgeig, Christopher B. Daniels, and David Palmer. Alterations in the surface properties of lung surfactant in the torpid marsupial Sminthopsis crassicaudata. J. Appl. Physiol. 84(1): 146–156, 1998.—Torpor changes the composition of pulmonary surfactant (PS) in the dunnart Sminthopsis crassicaudata [C. Langman, S. Orgeig, and C. B. Daniels. Am. J. Physiol. 271 ( Regulatory Integrative Comp. Physiol. 40): R437–R445, 1996]. Here we investigated the surface activity of PS in vitro. Five micrograms of phospholipid per centimeter squared surface area of whole lavage (from mice or from warm-active, 4-, or 8-h torpid dunnarts) were applied dropwise onto the subphase of a Wilhelmy-Langmuir balance at 20°C and stabilized for 20 min. After 4 h of torpor, the adsorption rate increased, and equilibrium surface tension (STeq), minimal surface tension (STmin), and the %area compression required to achieve STmin decreased, compared with the warm-active group. After 8 h of torpor, STmin decreased [from 5.2 ± 0.3 to 4.1 ± 0.3 (SE) mN/m]; %area compression required to achieve STmindecreased (from 43.4 ± 1.0 to 27.4 ± 0.8); the rate of adsorption decreased; and STeqincreased (from 26.3 ± 0.5 to 38.6 ± 1.3 mN/m). ST-area isotherms of warm-active dunnarts and mice at 20°C had a shoulder on compression and a plateau on expansion. These disappeared on the isotherms of torpid dunnarts. Samples of whole lavage (from warm-active and 8-h torpor groups) containing 100 μg phospholipid/ml were studied by using a captive-bubble surfactometer at 37°C. After 8 h of torpor, STmin increased (from 6.4 ± 0.3 to 9.1 ± 0.3 mN/m) and %area compression decreased in the 2nd (from 88.6 ± 1.7 to 82.1 ± 2.0) and 3rd (from 89.1 ± 0.8 to 84.9 ± 1.8) compression-expansion cycles, compared with warm-active dunnarts. ST-area isotherms of warm-active dunnarts at 37°C did not have a shoulder on compression. This shoulder appeared on the isotherms of torpid dunnarts. In conclusion, there is a strong correlation between in vitro changes in surface activity and in vivo changes in lipid composition of PS during torpor, although static lung compliance remained unchanged (see Langman et al. cited above). Surfactant from torpid animals is more active at 20°C and less active at 37°C than that of warm-active animals, which may represent a respiratory adaptation to low body temperatures of torpid dunnarts.


1994 ◽  
Vol 36 (1) ◽  
pp. 62A-62A
Author(s):  
Christian F Poets ◽  
Ilona Martin ◽  
Christa Acevedo ◽  
Kristin Neuber ◽  
Anne Rudolph ◽  
...  

2016 ◽  
Vol 256 ◽  
pp. 133-138 ◽  
Author(s):  
Marialaura Tocci ◽  
Christoph Zang ◽  
Ines Cadòrniga Zueco ◽  
Annalisa Pola ◽  
Michael Modigell

Rheological properties of liquid metals are difficult to investigate experimentally because of the extreme border conditions to consider. One difficulty is related to the low viscosity of liquid metals. Surface tension effects can cause forces that can be considerably higher than the viscous forces in the liquid metals. Evaluating the experimental data without considering these effects leads to an apparent shear thinning behavior of the material. In the present study, experiments were performed by means of a Searle rheometer changing the dimension of the measuring system with metals of high surface tension, as mercury and tin. It became evident that surface tension plays a significant role in the effects that falsify measurements at low shear rate. Conclusions can be drawn to what extent measurements of semi-solid metals are affected.


2014 ◽  
Vol 752 ◽  
pp. 410-438 ◽  
Author(s):  
J. O. Marston ◽  
S. T. Thoroddsen

AbstractWe present findings from an experimental investigation into the impact of solid cone-shaped bodies onto liquid pools. Using a variety of cone angles and liquid physical properties, we show that the ejecta formed during the impact exhibits self-similarity for all impact speeds for very low surface tension liquids, whilst for high-surface tension liquids similarity is only achieved at high impact speeds. We find that the ejecta tip can detach from the cone and that this phenomenon can be attributed to the air entrainment phenomenon. We analyse of a range of cone angles, including some ogive cones, and impact speeds in terms of the spatiotemporal evolution of the ejecta tip. Using superhydrophobic cones, we also examine the entry of cones which entrain an air layer.


The types of apparatus used to produce liquid sheets are classified according to the manner in which the energy is imparted to the liquid. The factors influencing the development, stability and manner of disintegration of a liquid sheet are examined more particularly with flat sheets produced from the single-hole fan-spray nozzle and the spinning disk. The development of the liquid sheet is influenced by the liquid properties. As the working pressure is raised the width of the sheet increases, but this development is hindered by high surface tension. It is shown that the effect of a surface-active agent on the development is only influential where the surface is not expanding or changing rapidly. Consequently its effect is more pronounced as the liquid moves farther away from the orifice. Increase of viscosity at the same pressure causes the region of disintegration to move away from the orifice, and high viscosity maintains the sheet undisturbed by air friction. Density has little effect on the area of the sheet. The effect of turbulence in the orifice is shown to be responsible for at least two types of disturbance in the sheet which results in holes being formed near the orifice. The depth of the disturbance in the sheet has to be equal to the thickness before disruption occurs. Similar disruption through the formation of holes can be caused by suspensions of unwettable particles. Wettable particles in low concentration, irrespective of their size, have no effect on the manner of disintegration. The most placid, stable and resistant sheet is obtained with a liquid of high surface tension, high viscosity, low density, giving low turbulence in the nozzle. Such a sheet will disintegrate when the velocity is raised and disintegration can occur through air friction. The easiest sheet to disintegrate is obtained with a liquid of low surface tension, low viscosity, low density and with low turbulence in the nozzle. Disintegration will occur near the nozzle at low velocities through waves caused by air friction. Disintegration through the formation of holes in the sheet can occur at low velocity with liquids of high surface-tension, low viscosity and high density where turbulence obtains in the nozzle. The formation of ligaments or threads is a necessary stage before the production of drops. Threads can be formed directly from any free edge or in the boundary. A free edge is formed when equilibrium exists between surface tension and inertia forces. In the spinning disk, at low flow rates, where the sheet is in contact with the surface of the disk, drops are formed at the ends of threads which break down into a limited number of sizes. At high flow rates a free edge of liquid exists outside the periphery of the disk with the formation of more irregular threads and a wider spectrum of drop sizes results. Where perforations occur in the sheet, expansion of the hole by surface tension occurs very regularly so that the holes remain nearly circular until they coalesce forming long threads. These long threads quickly become unstable and break down into drops. Threads being approximately uniform in diameter produce uniform drops, but the irregular areas of liquid which occur when a number of holes expand towards each other produce a wide variety of drop sizes. When the velocity of the sheet in the atmosphere is high, air friction causes slight variations in the sheet to develop rapidly into major wave disturbances, and these can result in holes being blown through the sheet so that disruption starts before the formation of a leading edge. With liquids having visco-elastic properties the sheet disintegrates through the formation of waves, but the rapid increase of viscosity, as the rate of shear is reduced, prevents further break-up of the threads into drops and a web of fine threads only is produced.


The interphase surface tension in superconducting aluminium has been measured using techniques previously applied to tin (Faber 1954). It proves to be several times larger than in the latter metal, besides varying rather differently with temperature and showing signs of an interesting dependence on specimen purity. The results are compared with predictions by Pippard (1951, 1953) and Bardeen (1954), and it is shown that the former theory, though less complete, is slightly more successful. On account of its high surface tension aluminium supercools to an unusual extent. In some cases it has been possible to reduce the applied field to 5 % of H c without nucleation occurring. This behaviour appears to be characteristic of the ideal, flawless metal, and it is explained in terms of a simple model based on the idea of coherence.


2015 ◽  
Vol 455 ◽  
pp. 1-5 ◽  
Author(s):  
Damena D. Agonafer ◽  
Ken Lopez ◽  
James W. Palko ◽  
Yoonjin Won ◽  
Juan G. Santiago ◽  
...  

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