Inhibition of pulmonary surfactant function by phospholipases

1991 ◽  
Vol 71 (1) ◽  
pp. 317-321 ◽  
Author(s):  
B. A. Holm ◽  
L. Keicher ◽  
M. Y. Liu ◽  
J. Sokolowski ◽  
G. Enhorning
Keyword(s):  
Surface Tension ◽  
Lung Injury ◽  
Pulmonary Surfactant ◽  
Detrimental Effect ◽  
Surface Film ◽  
Intratracheal Administration ◽  
Low Concentrations ◽  
Surfactant Activity ◽  
Inhibitory Agents ◽  
Biophysical Activity

Previous studies have shown that respiratory failure associated with disorders such as acute pancreatitis correlates well with increased levels of phospholipase A2 (PLA2) in lung lavages and that intratracheal administration of PLA2 generates an acute lung injury. In addition, bacteria such as Pseudomonas have been shown to secrete phospholipase C (PLC). We studied the effects of these phospholipases on pulmonary surfactant activity using a pulsating bubble surfactometer. Concentrations greater than or equal to 0.1 unit/ml PLA2 destroyed surfactant biophysical activity, increasing surface tension at minimum bubble size from less than 1 to 15 mN/m. This surfactant inactivation was predominantly related to the effect of lysophosphatidylcholine on the surface film, although the fatty acids released with higher PLA2 concentrations also had a detrimental effect on surfactant function. Similarly, as little as 0.1 unit PLC increased the surface tension at minimal size of an oscillating bubble from less than 1 to 15 mN/m, an effect that could be mimicked by the addition of dipalmitin to surfactant in the absence of PLC. Moreover, lower, noninhibitory concentrations (0.01 unit/ml) of PLA2 and PLC increased the sensitivity of surfactant to other inhibitory agents, such as albumin. Thus, relatively low concentrations of PLC and PLA2 can cause severe breakdown of surfactant function and may contribute significantly to some forms of lung injury.

scholarly journals Changes in respiratory elastance after deep inspirations reflect surface film functionality in mice with acute lung injury

2015 ◽  
Vol 119 (3) ◽  
pp. 258-265 ◽  
Author(s):  
Ayuko Takahashi ◽  
Erzsébet Bartolák-Suki ◽  
Arnab Majumdar ◽  
Béla Suki
Keyword(s):  
Surface Tension ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Surfactant ◽  
Surface Film ◽  
Lavage Fluid ◽  
Strong Negative Correlation ◽  
Alveolar Collapse ◽  
Rate Of Increase ◽  
Organ Level

Pulmonary surfactant reduces surface tension in the lung and prevents alveolar collapse. Following a deep inspiration (DI), respiratory elastance first drops then gradually increases due to surface film and tissue viscoelasticity. In acute lung injury (ALI), this increase is faster and governed by alveolar collapse due to increased surface tension. We hypothesized that the rate of increase in elastance reflects the deficiency of surfactant in the lung. To test this, mice were ventilated before (baseline) and after saline lavage obtained by injecting 0.8 ml and withdrawing 0.7 ml fluid (severe ALI) or injecting 0.1 ml (mild ALI). After two DIs, elastance was tracked for 10 min followed by a full lavage to assess surfactant proteins B (SP-B) and C (SP-C) content. Following 2 DIs, the increases in elastance during 10 min ventilation (Δ H) were 3.60 ± 0.61, 5.35 ± 1.04, and 8.33 ± 0.84 cmH2O/ml in baseline mice and mice with mild and severe ALI, respectively ( P < 0.0001). SP-B and SP-C in the lavage fluid dropped by 32.4% and 24.9% in the mild and 50.4% and 39.6% in the severe ALI, respectively. Furthermore, Δ H showed a strong negative correlation with both SP-B ( r2 = 0.801) and SP-C ( r2 = 0.810) content. The Δ H was, however, much smaller when the lavage fluid also contained exogeneous SP-B and SP-C. Thus Δ H can be interpreted as an organ level measure of surface film functionality in lavage-induced ALI in mice. This method could prove useful in clinical situations such as diagnosing surfactant problems, monitoring recovery from lung injury or the effectiveness of surfactant therapy.

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.

Dipalmitoyl lecithin: studies on surface properties

1965 ◽  
Vol 20 (4) ◽  
pp. 779-781 ◽  
Author(s):  
Marian C. Kuenzig ◽  
Robert W. Hamilton ◽  
Leonard F. Peltier
Keyword(s):  
Surface Tension ◽  
Pulmonary Surfactant ◽  
Surface Film ◽  
Ethanol Solution ◽  
Original Surface ◽  
Dipalmitoyl Lecithin ◽  
Minimum Surface Tension ◽  
Humidified Air ◽  
Surface Balance ◽  
Normal Lungs

A preparation of synthetic dipalmitoyl lecithin has been devised whose activity on a Wilhelmy surface balance is similar to that of extracts from normal lungs. An ethanol solution of lecithin is precipitated with albumin, and a drop of the suspension containing approximately 0.04 mg lecithin is spread on the surface of 0.9% NaCl in the trough of the balance. This preparation appears to be insensitive to oxidation and when run under humidified air gives reproducible results. It has a low minimum surface tension (5—10 dynes/cm) when compressed to 20% of the original surface area and exhibits considerable hysteresis on re-expansion. Addition of certain lipids to the surface film produces changes similar to those caused by addition of these lipids to cat lung extracts. surface tension; surface activity; pulmonary surfactant Submitted on September 8, 1964

Pulmonary surfactant

1984 ◽  
Vol 62 (11) ◽  
pp. 1121-1133 ◽  
Author(s):  
Fred Possmayer ◽  
Shou-Hwa Yu ◽  
J. Marnie Weber ◽  
Paul G. R. Harding
Keyword(s):  
Surface Tension ◽  
Pulmonary Surfactant ◽  
Liquid Interface ◽  
Biological Assays ◽  
Dipalmitoyl Phosphatidylcholine ◽  
Essential Properties ◽  
Surfactant Activity ◽  
Mammalian Lung ◽  
Reduce Surface Tension ◽  
Air Liquid Interface

The mammalian lung is stabilized by a specialized material, the pulmonary surfactant, which acts by reversibly reducing the surface tension at the air–liquid interface of the lung during breathing. Pulmonary surfactant contains approximately 90% lipid and 10% proteins. Dipalmitoyl phosphatidylcholine, the major lipid component, appears to be primarily responsible for the ability to reduce surface tension to near 0 dyn/cm (1 dyn = 10 μN). The other components of pulmonary surfactant promote the adsorption and spreading of this disaturated lecithin at the air–liquid interface. Surfactant activity can be accessed by physical and biological assays. Apparent discrepancies between the results obtained with the Wilhelmy plate surface balance and the pulsating bubble surfactometer have led to the suggestion that separate "protein-facilitated" (catalytic type) and "protein-mediated" (chemical type) processes may be involved in adsorption and (or) spreading at the different surfactant concentrations used with these two techniques. Artificial surfactants, which mimic the essential properties of the natural product with the pulsating bubble surfactometer, can be produced with synthetic lipids. Treatment of prematurely delivered infants suffering from the neonatal respiratory distress syndrome with lipid extracts of pulmonary surfactant leads to a marked improvement in gaseous exchange.

scholarly journals Microscale distribution and dynamic surface tension of pulmonary surfactant normalize the recruitment of asymmetric bifurcating airways

2017 ◽  
Vol 122 (5) ◽  
pp. 1167-1178 ◽  
Author(s):  
Eiichiro Yamaguchi ◽  
Liam P. Nolan ◽  
Donald P. Gaver
Keyword(s):  
Surface Tension ◽  
Lung Injury ◽  
Pulmonary Surfactant ◽  
Dynamic Surface Tension ◽  
Dependent Manner ◽  
Dynamic Surface ◽  
Ventilator Induced Lung Injury ◽  
Large Influence ◽  
The Impact

We investigate the influence of bifurcation geometry, asymmetry of daughter airways, surfactant distribution, and physicochemical properties on the uniformity of airway recruitment of asymmetric bifurcating airways. To do so, we developed microfluidic idealized in vitro models of bifurcating airways, through which we can independently evaluate the impact of carina location and daughter airway width and length. We explore the uniformity of recruitment and its relationship to the dynamic surface tension of the lining fluid and relate this behavior to the hydraulic (PHyd) and capillary (PCap) pressure drops. These studies demonstrate the extraordinary importance of PCap in stabilizing reopening, even in highly asymmetric systems. The dynamic surface tension of pulmonary surfactant is integral to this stability because it modulates PCap in a velocity-dependent manner. Furthermore, the surfactant distribution at the propagating interface can have a very large influence on recruitment stability by focusing surfactant preferentially to specific daughter airways. This implies that modification of the surfactant distribution through novel modes of ventilation could be useful in inducing uniformly recruited lungs, aiding in gas exchange, and reducing ventilator-induced lung injury. NEW & NOTEWORTHY The dynamic surface tension of pulmonary surfactant is integral to the uniformity of asymmetric bifurcation airway recruitments because it modulates capillary pressure drop in a velocity-dependent manner. Also, the surfactant distribution at the propagating interface can have a very large influence on recruitment stability by focusing surfactant preferentially to specific daughter airways. This implies that modification of the surfactant distribution through novel modes of ventilation could be useful in inducing uniformly recruited lungs, reducing ventilator-induced lung injury.

Clearance of surfactant lipids by neutrophils and macrophages isolated from the acutely inflamed lung

2002 ◽  
Vol 282 (2) ◽  
pp. L330-L339 ◽  
Author(s):  
Omar A. Quintero ◽  
Jo Rae Wright
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Surfactant ◽  
Lung Diseases ◽  
Fold Increase ◽  
Activated Macrophages ◽  
Intratracheal Administration ◽  
Air Liquid Interface ◽  
Number Of Cells

Pulmonary surfactant reduces surface tension at the lung air-liquid interface and defends the host against infection. Several lines of evidence show that surfactant levels are altered in animal models and patients with inflammatory or infectious lung diseases. We tested the hypothesis that cells responding to lung injury alter surfactant levels through increased phospholipid clearance. Acute lung injury was induced by intratracheal administration of lipopolysaccharide (LPS; Escherichia coli026:B6) into rats. LPS exposure resulted in a 12-fold increase in the number of cells isolated by lavage, the majority of which were neutrophils. Isolated macrophages and neutrophils from LPS-treated lungs internalized and degraded lipids in vitro, and LPS injury stimulated uptake by macrophages twofold. We estimate that lipid clearance by lavage cells in LPS-treated lungs could be enhanced 6- to 13-fold with both activated macrophages and increased numbers of neutrophils contributing to the process. These data show that the increased number of cells in the alveolar space after acute lung injury may lead to alterations in surfactant pools via enhanced clearance and degradation of lipids.

LUNG PHOSPHOLIPIDS AND SURFACE TENSION CORRELATIONS IN INFANTS WITH AND WITHOUT HYALINE MEMBRANE DISEASE AND IN ADULTS

PEDIATRICS ◽  
1967 ◽  
Vol 40 (1) ◽  
pp. 13-19
Author(s):  
George W. Brumley ◽  
W. Alan Hodson ◽  
Mary Ellen Avery
Keyword(s):  
Fatty Acids ◽  
Surface Tension ◽  
Pulmonary Surfactant ◽  
Saturated Fatty Acids ◽  
Hyaline Membrane Disease ◽  
Low Concentrations ◽  
Hyaline Membrane ◽  
Minimum Surface Tension ◽  
Wet Weight ◽  
High Concentrations

Infants who have died with hyaline membrane disease have low concentrations of pulmonary phospholipids and reduced concentrations of saturated fatty acids at the alpha position of lung phosphatidyl choline. There is a highly significant correlation (p&lt; .001) between levels below 12.6 mg of pulmonary phospholipid per gram wet weight lung and high minimum surface tension values of lung saline extracts. Infants without hyaline membrane disease have high concentrations of pulmonary phospholipids (22.3 mg per gram wet weight). Infants who recovered from HMD and died of other causes show values intermediate to those of HMD and non-HMD infants. The excess above the critical minimum noted here suggests a reservoir of pulmonary surfactant.

scholarly journals Consecutive daily administration of intratracheal surfactant and human umbilical cord-derived mesenchymal stem cells attenuates hyperoxia-induced lung injury in neonatal rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hsiu-Chu Chou ◽  
Chien-Hsiang Chang ◽  
Chien-Han Chen ◽  
Willie Lin ◽  
Chung-Ming Chen
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lung Injury ◽  
Umbilical Cord ◽  
Daily Administration ◽  
Vascular Density ◽  
Human Umbilical Cord ◽  
Neonatal Rats ◽  
Vegf Expression ◽  
Intratracheal Administration

Abstract Background Surfactant therapy is a standard of care for preterm infants with respiratory distress and reduces the incidence of death and bronchopulmonary dysplasia in these patients. Our previous study found that mesenchymal stem cells (MSCs) attenuated hyperoxia-induced lung injury and the combination therapy of surfactant and human umbilical cord-derived MSCs (hUC-MSCs) did not have additive effects on hyperoxia-induced lung injury in neonatal rats. The aim is to evaluate the effects of 2 consecutive days of intratracheal administration of surfactant and hUC-MSCs on hyperoxia-induced lung injury. Methods Neonatal Sprague Dawley rats were reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 14. On postnatal day 4, the rats received intratracheal injections of either 20 μL of normal saline (NS) or 20 μL of surfactant. On postnatal day 5, the rats reared in RA received intratracheal NS, and the rats reared in O2 received intratracheal NS or hUC-MSCs (3 × 104 or 3 × 105 cells). Six study groups were examined: RA + NS + NS, RA + surfactant + NS, O2 + NS + NS, O2 + surfactant + NS, O2 + surfactant + hUC-MSCs (3 × 104 cells), and O2 + surfactant + hUC-MSCs (3 × 105 cells). The lungs were excised for histological, western blot, and cytokine analyses. Results The rats reared in hyperoxia and treated with NS yielded significantly higher mean linear intercepts (MLIs) and interleukin (IL)-1β and IL-6 levels and significantly lower vascular endothelial growth factors (VEGFs), platelet-derived growth factor protein expression, and vascular density than did those reared in RA and treated with NS or surfactant. The lowered MLIs and cytokines and the increased VEGF expression and vascular density indicated that the surfactant and surfactant + hUC-MSCs (3 × 104 cells) treatment attenuated hyperoxia-induced lung injury. The surfactant + hUC-MSCs (3 × 105 cells) group exhibited a significantly lower MLI and significantly higher VEGF expression and vascular density than the surfactant + hUC-MSCs (3 × 104 cells) group did. Conclusions Consecutive daily administration of intratracheal surfactant and hUC-MSCs can be an effective regimen for treating hyperoxia-induced lung injury in neonates.

scholarly journals TLR4-dependent GM-CSF protects against lung injury in Gram-negative bacterial pneumonia

2012 ◽  
Vol 302 (5) ◽  
pp. L447-L454 ◽  
Author(s):  
Louis R. Standiford ◽  
Theodore J. Standiford ◽  
Michael J. Newstead ◽  
Xianying Zeng ◽  
Megan N. Ballinger ◽  
...  
Keyword(s):  
Lung Injury ◽  
Bacterial Pneumonia ◽  
Lavage Fluid ◽  
Alveolar Epithelial Cells ◽  
Intratracheal Administration ◽  
Bacterial Colony ◽  
Gram Negative ◽  
Gm Csf

Toll-like receptors (TLRs) are required for protective host defense against bacterial pathogens. However, the role of TLRs in regulating lung injury during Gram-negative bacterial pneumonia has not been thoroughly investigated. In this study, experiments were performed to evaluate the role of TLR4 in pulmonary responses against Klebsiella pneumoniae (Kp). Compared with wild-type (WT) (Balb/c) mice, mice with defective TLR4 signaling (TLR4lps-d mice) had substantially higher lung bacterial colony-forming units after intratracheal challenge with Kp, which was associated with considerably greater lung permeability and lung cell death. Reduced expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA and protein was noted in lungs and bronchoalveolar lavage fluid of TLR4 mutant mice postintratracheal Kp compared with WT mice, and primary alveolar epithelial cells (AEC) harvested from TLR4lps-d mice produced significantly less GM-CSF in vitro in response to heat-killed Kp compared with WT AEC. TLR4lps-d AEC underwent significantly more apoptosis in response to heat-killed Kp in vitro, and treatment with GM-CSF protected these cells from apoptosis in response to Kp. Finally, intratracheal administration of GM-CSF in TLR4lps-d mice significantly decreased albumin leak, lung cell apoptosis, and bacteremia in Kp-infected mice. Based on these observations, we conclude that TLR4 plays a protective role on lung epithelium during Gram-negative bacterial pneumonia, an effect that is partially mediated by GM-CSF.

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