Differential permeability of endothelial and epithelial barriers to albumin flux

1979 ◽  
Vol 47 (6) ◽  
pp. 1315-1324 ◽  
Author(s):  
A. B. Gorin ◽  
P. A. Stewart
Keyword(s):  
Specific Activity ◽  
Membrane Damage ◽  
Endothelial Permeability ◽  
Lavage Fluid ◽  
Edema Formation ◽  
Lung Epithelial ◽  
Albumin Content ◽  
Epithelial Barriers ◽  
Lung Epithelial Permeability ◽  
Lung Lymph

We measured the flux of albumin between the vascular space and the pulmonary interstitial and luminal lining fluids in 20 adult sheep with chronic lung lymph fistulas. We sampled the bronchoalveolar lining layer by episodic fiberbronchoscopic lavage. A total of 62 alveolar lavages were performed at times ranging between 30 min and 60 h after intra-arterial injection of 100 microCi of 125I-labeled albumin. Samples of lymph and plasma were obtained simultaneously with lavage fluid, and the radioactivity and albumin content of all samples were measured and expressed as specific activity (counts/min . g albumin). We found that alveolar lavage fluid collected by our technique is not significantly contaminated by plasma or interstitial fluid proteins. Proteins present in alveolar lavage fluid and also present in plasma reach the alveolar space by a normal diffusive process, and not as a result of epithelial membrane damage occurring at the time of lavage. Lung epithelial permeability to albumin in small, but finite (4.3--5.8 x 10(-10) cm/s). Virtually all (greater than 92%) of resistance to albumin flux across the alveolocapillary membrane lies in the epithelial barrier. Increases in permeability of the respiratory epithelium, even minor, would have a marked effect on water and solute balance in the lung. Epithelial injury will potentiate pulmonary edema formation even in the presence of normal pulmonary microvascular pressure, plasma oncotic pressure, and endothelial permeability.

Role of lymphatics in removal of sheep lung surfactant lipid

1983 ◽  
Vol 54 (4) ◽  
pp. 984-988 ◽  
Author(s):  
M. M. Tarpey ◽  
H. M. O'Brodovich ◽  
S. L. Young
Keyword(s):  
Lung Tissue ◽  
Specific Activity ◽  
Mediastinal Lymph Node ◽  
Lung Surfactant ◽  
Lavage Fluid ◽  
Tissue Lipids ◽  
Surfactant Lipid ◽  
Lymph Lipid ◽  
Lung Lymph

To study the role of lung lymphatics in the removal of surfactant lipid from the sheep lung, we injected [1–14C]palmitate intravenously into six animals previously fitted with a cannula draining the caudal mediastinal lymph node. Lung lymph was collected for 100 h after injection of radiolabel. We obtained alveolar lavage material through a tracheostomy in four other animals after intravenous injection of [9,10–3H]palmitate. We measured radioactivity at several time points in lipid extracts from lymph, lavage fluid, and lung tissue. Alveolar lavage disaturated phosphatidylcholine (DSPC) specific activity peaked at about 40 h and was reduced to 30% of this value by 82 h. About 2% of the injected radiolabel was incorporated into lung tissue lipids. Only 4% of the level of labeling achieved in lung tissue lipids was found in lung lymph lipid during 100 h of lymph collection. Sixty-three percent of radiolabel in lymph lipid was recovered in phospholipids, and 29% of phospholipid radiolabel was found in DSPC. The distribution of phosphorus and palmitate radiolabel in lung lymph phospholipid did not closely resemble that of surfactant lipid. No rise in lung lymph DSPC specific activity was observed following the peak in lavage specific activity. If surfactant lipid is removed from the alveolar compartment without extensive recycling, then we conclude that the lung lymphatics do not play a major role in the clearance of surfactant lipid from the alveolar surface.

ANF decreases active sodium transport and increases alveolar epithelial permeability in rats

1993 ◽  
Vol 75 (4) ◽  
pp. 1581-1586 ◽  
Author(s):  
W. Olivera ◽  
K. Ridge ◽  
L. D. Wood ◽  
J. I. Sznajder
Keyword(s):  
Pulmonary Circulation ◽  
Lung Edema ◽  
Epithelial Permeability ◽  
Na Transport ◽  
Edema Formation ◽  
Alveolar Epithelial ◽  
Lung Epithelial ◽  
Air Space ◽  
Lung Epithelial Permeability ◽  
Reduced Pressures

Previous studies reported that atrial natriuretic factor (ANF) decreased lung edema in guinea pigs. To determine whether ANF protects against lung edema by increasing active Na+ transport and lung edema clearance, ANF (10(-7) M) was instilled into the air spaces (n = 5) or perfused through the pulmonary circulation (n = 5) of isolated perfused liquid-filled rat lungs. These animals were compared with five control rats and four rats having amiloride (10(-5) M) instilled into the air space. Amiloride reduced lung edema clearance by 65%, perfused ANF reduced lung edema clearance by 32%, and instilled ANF did not change edema clearance compared with responses in control rats after 70 min of experimental protocol. Passive Na+ movement increased by 91% with perfused ANF and by 52% with instilled ANF compared with that in control rats. Albumin flux from the perfusate into the air space increased in ANF-perfused lungs compared with control lungs (P < 0.05) but not when ANF or amiloride was instilled into the air spaces. These results suggest that ANF instilled into rat air spaces or perfused through the pulmonary circulation increases lung epithelial permeability and that ANF perfused through the pulmonary circulation decreases lung edema clearance due to impaired active Na+ transport. Conceivably, the previously observed protective effect of ANF was due to reduced pressures across the pulmonary circulation, which resulted in less edema formation.

Intravenous recombinant secretory leukoprotease inhibitor augments antineutrophil elastase defense

1992 ◽  
Vol 73 (1) ◽  
pp. 317-323 ◽  
Author(s):  
P. Birrer ◽  
N. G. McElvaney ◽  
A. Gillissen ◽  
R. F. Hoyt ◽  
D. C. Bloedow ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Lung Diseases ◽  
Effective Means ◽  
Upper Airway ◽  
Airway Epithelial ◽  
Epithelial Surface ◽  
Epithelial Lining Fluid ◽  
Lung Epithelial ◽  
Lung Lymph ◽  
Protective Screen

Secretory leukoprotease inhibitor (SLPI), a 12-kDa serine antiprotease, normally protects the upper airway epithelial surface from attack by neutrophil elastase (NE). In the context that a variety of inflammatory lung diseases are characterized by large neutrophil burdens with resultant high levels of NE in the lung, recombinant SLPI (rSLPI), a molecule identical to natural SLPI, may be an effective means to augment the anti-NE protective screen of the lung. To determine whether intravenous rSLPI will augment respiratory tract and epithelial surface levels of SLPI and anti-NE capacity, rSLPI was administered intravenously to sheep and SLPI levels were quantified in plasma, lung lymph (as a measure of lung interstitial levels), lung epithelial lining fluid (ELF), and urine. rSLPI (1 g) was administered over 10 min, and after 30 min plasma levels of SLPI were 8 microM and decreased with a half-life of 1.8 h. Lymph SLPI levels paralleled the plasma levels: 4 h after infusion the lymph-to-plasma ratio was 0.8. ELF SLPI levels paralleled the lymph levels: 4 h after infusion the ELF-to-lymph ratio was 0.3. Western analysis demonstrated intact SLPI in lymph and ELF, and functional analysis showed increases in lymph and ELF anti-NE capacity that paralleled the levels of SLPI. As might be expected from a protein with a molecular mass of 12 kDa, urine excretion was high, with 20% of the SLPI excreted over 5 h. However, if the rate of infusion was slowed, SLPI excretion decreased significantly, with a 3-h infusion associated with 9% excretion and a 12-h infusion associated with less than 0.2% excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

alpha-Trinositol decreases lung edema formation after smoke inhalation in an ovine model

1994 ◽  
Vol 76 (1) ◽  
pp. 278-282 ◽  
Author(s):  
H. Nakazawa ◽  
T. O. Gustafsson ◽  
L. D. Traber ◽  
D. N. Herndon ◽  
D. L. Traber
Keyword(s):  
Thermal Injury ◽  
Sham Group ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Lung Edema ◽  
Ovine Model ◽  
Edema Formation ◽  
Surgical Preparation ◽  
Lung Lymph ◽  
Lung Lymph Flow

Inhalation injury is a dominant cause of mortality in thermally injured individuals. After acute lung injury induced by smoke inhalation, lung lymph flow (QL) increased and pulmonary microvascular reflection coefficient to protein (sigma) decreased. alpha-Trinositol (PP56, 1D-myo-inositol 1,2,6-trisphosphate) can decrease edema formation after thermal injury. We therefore tested the hypothesis that alpha-trinositol could decrease the pulmonary edema noted with inhalation injury. Seven days after surgical preparation, sheep were insufflated with smoke from burning cotton towels. The alpha-trinositol group (n = 8) were treated with alpha-trinositol (2 mg/kg + 3.5 mg.kg-1 x h-1). The sham group (n = 7) received an equal volume of 0.9% NaCl. The sham group showed a large increase in QL (9.3 +/- 1.7 to 54.1 +/- 8.8 ml/h) and a decrease in sigma (0.79 +/- 0.03 to 0.48 +/- 0.03) 24 h after smoke inhalation. alpha-Trinositol attenuated the increase in QL (8.1 +/- 1.2 to 25.6 +/- 6.9 ml/h) and the decrease in sigma (0.76 +/- 0.03 to 0.60 +/- 0.03) noted with smoke inhalation. alpha-Trinositol thus decreased the changes in pulmonary microvascular permeability and transvascular fluid flux noted with inhalation injury.

scholarly journals Quinones increase γ-glutamyl transpeptidase expression by multiple mechanisms in rat lung epithelial cells

1998 ◽  
Vol 274 (3) ◽  
pp. L330-L336 ◽  
Author(s):  
Rui-Ming Liu ◽  
Michael Ming Shi ◽  
Cecilia Giulivi ◽  
Henry Jay Forman
Keyword(s):  
Specific Activity ◽  
Lung Epithelial Cells ◽  
Secondary Response ◽  
Protein Synthesis Inhibitor ◽  
Rat Lung ◽  
Synthesis Inhibitor ◽  
Lung Epithelial ◽  
Mrna Content ◽  
Gsh Metabolism ◽  
Glutamyl Transpeptidase

γ-Glutamyl transpeptidase (GGT) plays an important role in glutathione (GSH) metabolism. GGT expression is increased in oxidant-challenged cells; however, the signaling mechanisms involved are uncertain. The present study used 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), a redox cycling quinone that continuously produced H2O2in rat lung epithelial L2 cells. It was found that DMNQ increased GGT mRNA content by increasing transcription, as measured by nuclear run-on. This was accompanied by increased GGT specific activity. Cycloheximide, a protein synthesis inhibitor, blocked neither the increased GGT mRNA content nor the increased GGT transcription rate caused by DMNQ, suggesting that increased GGT transcription was a direct rather than secondary response. Previous data from this laboratory (R.-M. Liu, H. Hu, T. W. Robison, and H. J. Forman. Am. J. Respir. Cell Mol. Biol.14: 186–191, 1996) showed that tert-butylhydroquinone (TBHQ) increased GGT mRNA content by increasing its stability. TBHQ differs markedly from DMNQ in terms of its conjugation with GSH and H2O2generation. Together, the data suggest that quinones upregulate GGT through multiple mechanisms, increased transcription and posttranscriptional modulation, which are apparently mediated through generation of reactive oxygen species and GSH conjugate formation, respectively.

scholarly journals Effects of tidal volume and respiratory frequency on lung lymph flow

2005 ◽  
Vol 99 (2) ◽  
pp. 556-563 ◽  
Author(s):  
David B. Pearse ◽  
Robert M. Searcy ◽  
Wayne Mitzner ◽  
Solbert Permutt ◽  
J. T. Sylvester
Keyword(s):  
Tidal Volume ◽  
Lymphatic Vessels ◽  
Lymph Flow ◽  
Edema Formation ◽  
Fluid Filtration ◽  
Induced Changes ◽  
Lung Lymph ◽  
Lung Lymph Flow

Ventilation (V̇) increases lung lymph flow (Q̇l), but the separate effects of tidal volume (Vt) and frequency (f) and the role of V̇-induced changes in edema formation are poorly understood. An isolated, in situ sheep lung preparation was used to examine these effects. In eight sheep with f = 10 min−1, results obtained during 30-min periods with Vt = 5 or 20 ml/kg were compared with values obtained during bracketed 30-min control periods (Vt = 12.5 ml/kg). Eight other sheep with constant Vt (12.5 ml/kg) were studied at f = 5 or 20 min−1 and compared with f = 10 min−1. Three additional groups of six sheep were perfused for 100 min with control V̇ (10 ml/kg, 10 min−1). Vt was then kept constant or changed to 20 or 3 ml/kg during a second 100-min period. Increases in Vt or f increased Q̇l and vice versa, without corresponding effects on the rate of edema formation. For the same change in V̇, changing Vt had a greater effect on Q̇l than changing f. The change in Q̇l caused by an increase in Vt was significantly greater after the accumulation of interstitial edema. The change in Q̇l caused by a sustained increase in Vt was transient and did not correlate with the rate of edema formation, suggesting that V̇ altered Q̇l through direct mechanical effects on edema-filled compartments and lymphatic vessels rather than through V̇-induced changes in fluid filtration.

Differential effects of salmeterol on lung endothelial and epithelial leakage in sheep

1996 ◽  
Vol 80 (5) ◽  
pp. 1666-1673 ◽  
Author(s):  
B. T. Peterson ◽  
D. E. Griffith ◽  
J. C. Connelly ◽  
R. W. Tate
Keyword(s):  
Endothelial Permeability ◽  
Lymph Flow ◽  
Arterial Oxygen ◽  
Water Volume ◽  
Epithelial Lining ◽  
Lung Water ◽  
Protein Ratio ◽  
Epithelial Lining Fluid ◽  
Control Value ◽  
Lung Epithelial Permeability

Salmeterol has been shown to prevent the influx of proteins into the air spaces of lungs of guinea pigs given intravenous histamine. To determine whether the salmeterol acts to stabilize the epithelial or endothelial barrier, we ventilated anesthetized sheep with aerosolized salmeterol before infusing histamine intravenously at a rate of 4 micrograms.kg-1.min-1 for 3 h. Changes in endothelial permeability were assessed by measuring the flow of lymph and proteins from the lungs. The influx of proteins into the air spaces was detected by performing single-cycle lavages to measure the concentration of circulating 125I-albumin in the epithelial lining fluid. Intravenous histamine increased the lymph flow to 13.2 +/- 6.8 ml/h compared with the control value of 5.6 +/- 2.8 ml/h (P < 0.05). Histamine also increased the concentration of 125I-albumin in the epithelial lining fluid from 1.8 +/- 0.9 to 8.5 +/- 2.5% of the plasma concentration (P < 0.01) and the postmortem lung water volume from 3.5 +/- 0.5 to 5.0 +/- 0.8 mg/g dry lung wt (P < 0.05). Pretreatment with 2.5 mg of aerosolized salmeterol prevented the influx of proteins into the air spaces and the increase in the postmortem lung water volume but it also increased the lung lymph flow even further to 20.0 +/- 5.6 ml/h (P < 0.05), increased the lymph-to-plasma protein ratio from 0.77 to 0.91, and tripled the increase in alveolar-arterial oxygen gradient caused by histamine alone. Pretreatment with 2.5 mg of intravenous salmeterol had essentially the same effect as salmeterol administered by aerosol. We conclude that salmeterol decreases lung epithelial permeability but increases lung endothelial permeability due to intravenous histamine in sheep.

Asbestos-induced lung epithelial permeability: potential role of nonoxidant pathways

1998 ◽  
Vol 275 (2) ◽  
pp. L262-L268
Author(s):  
Michael W. Peterson ◽  
Jennifer Kirschbaum
Keyword(s):  
Tyrosine Kinase ◽  
Lung Fibrosis ◽  
Human Lung ◽  
Biological Effects ◽  
Tyrosine Phosphatase ◽  
Epithelial Permeability ◽  
Lung Epithelium ◽  
Asbestos Fibers ◽  
Lung Epithelial ◽  
Lung Epithelial Permeability

Asbestos fibers are an important cause of lung fibrosis; however, the biological mechanisms are incompletely understood. The lung epithelium serves an important barrier function in the lung, and disrupting the epithelial barrier can contribute to lung fibrosis. Lung epithelial permeability is increased in patients with asbestosis, and asbestos fibers increase permeability across cultured human lung epithelium. However, the mechanism of this increased permeability is not known. Many of the biological effects of asbestos are postulated to be due to its ability to generate oxidants, and oxidants are known to increase epithelial permeability. However, we previously reported that altering the iron content of asbestos (important in oxidant generation) had no effect on its ability to increase permeability. For that reason, we undertook these studies to determine whether asbestos increases epithelial permeability through nonoxidant pathways. Both extracellular (H2O2) and intracellular (menadione) oxidants increase paracellular permeability across human lung epithelial monolayers. Extracellular catalase but not superoxide dismutase prevented increased permeability after both oxidant exposures. However, catalase offered no protection from asbestos-induced permeability. We next depleted the cells of glutathione or catalase to determine whether depleting normal cellular antioxidants would increase the sensitivity to asbestos. Permeability was the same in control cells and in cells depleted of these antioxidants. In addition to generating oxidants, asbestos also activates signal transduction pathways. Blocking protein kinase C activation did not prevent asbestos-induced permeability; however, blocking tyrosine kinase with tyrophostin A25 did prevent asbestos-induced permeability, and blocking tyrosine phosphatase with sodium vanadate enhanced the effect of asbestos. These data demonstrate that asbestos may increase epithelial permeability through nonoxidant pathways that involve tyrosine kinase activation. This model offers an important system for studying pathways involved in regulating lung epithelial permeability.

Lung epithelial permeability: relation to nonspecific airway responsiveness

1984 ◽  
Vol 57 (1) ◽  
pp. 77-84 ◽  
Author(s):  
P. M. O'Byrne ◽  
M. Dolovich ◽  
R. Dirks ◽  
R. S. Roberts ◽  
M. T. Newhouse
Keyword(s):  
Airway Responsiveness ◽  
Epithelial Permeability ◽  
Lung Epithelial ◽  
Lung Epithelial Permeability
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