The late asthmatic response is linked with increased surface tension and reduced surfactant protein B in mice

2002 ◽  
Vol 283 (4) ◽  
pp. L755-L765 ◽  
Author(s):  
Angela Haczku ◽  
Elena N. Atochina ◽  
Yaniv Tomer ◽  
Yang Cao ◽  
Colleen Campbell ◽  
...  
Keyword(s):  
Surface Tension ◽  
Pulmonary Surfactant ◽  
Late Phase ◽  
Surfactant Protein ◽  
Intratracheal Administration ◽  
Asthmatic Response ◽  
Surfactant Protein B ◽  
Airway Response ◽  
Allergen Provocation ◽  
Surfactant Dysfunction

Pulmonary surfactant dysfunction may significantly contribute to small airway obstruction during the asthmatic response, but neither its exact role nor its regulation is clear. Surfactant function and composition was studied in an Aspergillus fumigatus ( Af)-induced late-phase allergic airway response in sensitized BALB/c mice. The peak of Af-induced airway hyperresponsiveness in sensitized and challenged mice 24 h after allergen provocation coincided with a significant fall in surface activity of the pulmonary surfactant. The underlying changes included time-dependent elaboration of eotaxin and IL-5 followed by eosinophil influx into the airways. The height of airway inflammation and hyperresponsiveness was preceded by release of IL-4 and marked reductions in surfactant protein (SP)-B, a hydrophobic surfactant protein responsible for maintaining low surface tension of the lining fluid of distal air spaces. Furthermore, intratracheal administration of IL-4 significantly inhibited SP-B, indicating a regulatory role of this cytokine in the surfactant biophysical changes. Thus surfactant dysfunction induced by an IL-4-driven SP-B deficiency after allergen provocation may be an important part of the late asthmatic airway response.

scholarly journals Surfactant Protein B Deficiency Induced High Surface Tension: Relationship between Alveolar Micromechanics, Alveolar Fluid Properties and Alveolar Epithelial Cell Injury

2019 ◽  
Vol 20 (17) ◽  
pp. 4243 ◽  
Author(s):  
Nina Rühl ◽  
Elena Lopez-Rodriguez ◽  
Karolin Albert ◽  
Bradford J Smith ◽  
Timothy E Weaver ◽  
...  
Keyword(s):  
Surface Tension ◽  
Lung Injury ◽  
High Surface ◽  
Surfactant Protein ◽  
Epithelial Injury ◽  
High Surface Tension ◽  
Alveolar Epithelial ◽  
Surfactant Protein B ◽  
Fluid Properties ◽  
Alveolar Epithelial Injury

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.

Glucocorticoid enhances pulmonary surfactant protein B gene transcription

1991 ◽  
Vol 260 (2) ◽  
pp. L37-L43 ◽  
Author(s):  
M. A. O'Reilly ◽  
J. C. Clark ◽  
J. A. Whitsett
Keyword(s):  
Protein Synthesis ◽  
Cell Line ◽  
Gene Transcription ◽  
Pulmonary Surfactant ◽  
Actinomycin D ◽  
Surfactant Protein ◽  
Surfactant Protein B ◽  
Pulmonary Surfactant Protein B ◽  
Pulmonary Surfactant Protein ◽  
Protein B

The effect of glucocorticoid on the regulation of pulmonary surfactant protein B (SP-B) synthesis was studied in a human pulmonary adenocarcinoma cell line. Northern blot analysis demonstrated a marked increase in SP-B mRNA expression after treatment with dexamethasone for 48 h. Actinomycin D, puromycin, or cycloheximide blocked the induction of SP-B mRNA by glucocorticoid. Nuclear run-on experiments demonstrated that the effects of dexamethasone on SP-B mRNA were due in part to increased transcription of the SP-B gene. However, during this time period, there was a discrepancy between SP-B gene transcription, which was increased only 2- to 4-fold, and SP-B mRNA, which increased 60- to 150-fold after treatment with dexamethasone. In the presence of actinomycin D, SP-B mRNA was relatively stable, decreasing slowly in the presence or absence of glucocorticoid. In contrast to the relative stability of SP-B mRNA in the presence of actinomycin D, SP-B mRNA was markedly decreased after exposure to puromycin, supporting the premise that continued protein synthesis, rather than transcription alone, is required for maintenance of SP-B mRNA levels. Induction of SP-B expression by glucocorticoids was dependent on enhanced SP-B gene transcription and was also dependent on continued protein synthesis. The discrepancy between the relative enhancement of SP-B transcription and SP-B mRNA suggests that posttranscriptional factors influence SP-B expression in this cell line.

An En Bloc Staining Protocol Improves The Preservation of Lamellar Bodies in Alveolar Type II Epithelial Cells for Transgenic Mice Expressing Modified Pulmonary Surfactant Protein B

1998 ◽  
Vol 4 (S2) ◽  
pp. 852-853
Author(s):  
C.-L. Na ◽  
D. C. Beck ◽  
J. S. Breslin ◽  
S. E. Wert ◽  
T. E. Weaver
Keyword(s):  
Pulmonary Surfactant ◽  
Surfactant Protein ◽  
Alveolar Type ◽  
Type Ii ◽  
Lamellar Bodies ◽  
En Bloc ◽  
Surfactant Protein B ◽  
Staining Protocol ◽  
Pulmonary Surfactant Protein B ◽  
Pulmonary Surfactant Protein

The extraction of lipids and phospholipids during dehydration and plastic embedding steps results in poor preservation of the phospholipid rich lamellar bodies (LB) in alveolar type II epithelial cells. To achieve better retention of phospholipids, we combined inflation fixation and an en bloc staining protocol using 4% aqueous uranyl acetate (UA), thereby improving the preservation of the LBs for both the wild type and transgenic mice expressing modified pulmonary surfactant protein B (SP-B; Akinbi et al., 1997).Lungs of 6-8 week-old mice were inflation fixed (Bunkingham and Weyder, 1981) with ice cold 2% paraformaldehye and 2% glutaraldehyde in 0.1 M sodium cacodylate buffer (SCB), pH 7.3, postfixed in fresh fixative at 4 °C overnight, incubated with 1% osmium tetroxide in 0.1 M SCB at room temperature for 2 hours, and stained en bloc with 4% aqueous UA overnight.

Decreased Surfactant Protein-B Expression and Surfactant Dysfunction in a Murine Model of Acute Lung Injury

2001 ◽  
Vol 25 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Edward P. Ingenito ◽  
Rene Mora ◽  
Michael Cullivan ◽  
Yolanda Marzan ◽  
Kathleen Haley ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Murine Model ◽  
Surfactant Protein ◽  
Surfactant Protein B ◽  
Surfactant Dysfunction ◽  
Protein B

scholarly journals Glucocorticoid regulation of human pulmonary surfactant protein-B (SP-B) mRNA stability is independent of activated glucocorticoid receptor

2011 ◽  
Vol 300 (6) ◽  
pp. L940-L950 ◽  
Author(s):  
Ceá C. Tillis ◽  
Helen W. Huang ◽  
Weizhen Bi ◽  
Su Pan ◽  
Shirley R. Bruce ◽  
...  
Keyword(s):  
Steady State ◽  
Glucocorticoid Receptor ◽  
Mrna Stability ◽  
Pulmonary Surfactant ◽  
Surfactant Protein ◽  
Airway Epithelial Cells ◽  
Mrna Levels ◽  
Airway Epithelial ◽  
Surfactant Protein B ◽  
Steady State Levels

Adequate expression of surfactant protein-B (SP-B) is critical in the function of pulmonary surfactant to reduce alveolar surface tension. Expression of SP-B mRNA is restricted to specific lung-airway epithelial cells, and human SP-B mRNA stability is increased in the presence of the synthetic glucocorticoid dexamethasone (DEX). Although the mechanism of SP-B mRNA stabilization by DEX is unknown, studies suggest involvement of the glucocorticoid receptor (GR). We developed a dual-cistronic plasmid-based expression assay in which steady-state levels of SP-B mRNA, determined by Northern analysis, reproducibly reflect changes in SP-B mRNA stability. Using this assay, we found that steady-state levels of SP-B mRNA increased greater than twofold in transfected human-airway epithelial cells (A549) incubated with DEX (10−7 M). DEX-mediated changes in SP-B mRNA levels required the presence of the SP-B mRNA 3′-untranslated region but did not require ongoing protein synthesis. The effect of DEX on SP-B mRNA levels was dose dependent, with maximal effect at 10−7 M. DEX increased levels of SP-B mRNA in cells lacking GR, and the presence of the GR antagonist RU486 did not interfere with the effect of DEX. Surprisingly, other steroid hormones (progesterone, estradiol, and vitamin D; 10−7 M) significantly increased SP-B mRNA levels, suggesting a common pathway of steroid hormone action on SP-B mRNA stability. These results indicate that the effect of DEX to increase SP-B mRNA stability is independent of activated GR and suggests that the mechanism is mediated by posttranscriptional or nongenomic effects of glucocorticoids.

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