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PubMed2000

Degree of lung maturity determines the direction of the interleukin-1- induced effect on the expression of surfactant proteins.

Intra-amniotic interleukin (IL)-1 increases surfactant components in immature fetal lung, whereas high IL-1 after birth is associated with surfactant dysfunction. Our aim was to investigate whether the fetal age influences the responsiveness of surfactant proteins (SPs) to IL-1. Rabbit lung explants from fetuses at 19, 22, 27, and 30 d of gestation and 1-d-old newborns were cultured in serum-free medium in the presence of recombinant human (rh) IL-1alpha or vehicle. The influence of IL-1alpha on SP-A, -B, and -C messenger RNA (mRNA) content was dependent on the conceptional age. In very immature lung on Day 19, rhIL-1alpha (570 ng/ml for 20 h) increased SP-A, -B, and -C mRNA by 860+/-15%, 314+/-108%, and 64+/-17%, respectively. The increase in SP-A mRNA was evident within 4 to 6 h. IL-1alpha increased the SP-A concentration in alveolar epithelial cells and in the culture medium within 20 h. In contrast, at 27 to 30 d of gestation and in newborns, IL-1alpha decreased SP-C, -B, and -A mRNA by means of 64 to 67%, 48 to 59%, and 12 to 15%, respectively. SP-B protein decreased by 45 to 60%. The decrease in mRNA became evident within 8 to 12 h and was dependent on IL-1 concentration. On Day 27, IL-1alpha accelerated the degradation of SP-B mRNA in the presence of actinomycin D. IL-1 did not increase the degradation rate of SP-A mRNA unless both actinomycin D and cycloheximide were added to the explants. The present findings may explain some of the contrasting associations between inflammatory cytokines and lung diseases during the perinatal period. The determinants of the direction of the IL-1 effect on the expression of SPs remain to be identified.

Amniotic Fluid↗

PubMed2000

[Pulmonary surfactant in the respiratory tract].

Pulmonary surfactant is a surface active material able to reduce surface tension at the alveolar and bronchiolar air-liquid interface. It plays an important role in conductive as well in peripheral airways and that is why surfactant dysfunction is thought to contribute to pathomechanisms of pulmonary diseases with bronchial obstruction. Airway surfactant originates mainly from alveoli and some components (specific proteins SP-A, SP-B and SP-D) are synthetized and secreted also by non-ciliated cells of the airway mucosa. In comparison to alveolar surfactant the bronchiol one has the same composition, with lower amount of surfactant proteins. Surfactant has following functions in airways: stabilisation of small airways, role in mucociliary and non-ciliary transport, immunomodulation, barrier function and antiedematous function. Ability of pulmonary surfactant to influence wall thickness and diameter of airways indicates possible role of its quantitative and/or qualitative changes in the pathogenesis of asthma, chronic obstructive pulmonary disease and others.

Humans↗

PubMed1994

Natural surfactant and hyperoxic lung injury in primates. I. Physiology and biochemistry.

Surfactant dysfunction contributes to the pathophysiology of adult respiratory distress syndrome (ARDS), and we hypothesized that surfactant treatment would improve experimental ARDS produced by continuous exposure to hyperoxia. Twelve healthy male baboons (10-15 kg) were anesthetized, paralyzed, and mechanically ventilated with 2.5 cmH2O positive end-expiratory pressure (PEEP) for 96 h. Baboons were divided into three groups: 1) the O2 group (n = 5) received 100% O2, 2) the surfactant group (n = 5) received 100% O2 and aerosolized porcine surfactant, and 3) a control group (n = 2) was ventilated at fractional concentration of inspired O2 of 0.21 for 96 h to control for effects of anesthesia and mechanical ventilation. Hemodynamic parameters were obtained every 12 h, and ventilation-perfusion (VA/Q) distribution was measured daily by multiple inert gas elimination technique. PEEP was increased once or twice daily to 10 cmH2O for 30 min to study its effects on measurements of VA/Q. At the end of experiments, lungs were obtained for biochemical analysis. Prolonged hyperoxia resulted in progressive worsening in VA/Q, hemodynamic deterioration, severe lung edema, and altered surfactant metabolism. Surfactant administration increased disaturated phosphatidylcholine in lavage fluid but did not improve lung edema or gas exchange. In the surfactant group, however, the addition of 10 cmH2O PEEP resulted in a greater degree of shunt reduction than did 2.5 cmH2O PEEP (47 vs. 31% in the O2 group, P < 0.05). We conclude that aerosolized porcine surfactant did not prevent pulmonary O2 injury in baboons, but it potentiated the shunt-reducing effect of PEEP.

Aerosols↗

PubMed1997

Effect of surfactant inhalation on allergic bronchoconstriction in guinea pigs.

BACKGROUND: In the small airway, surfactant reduces surface tension, prevents liquid filling of bronchioles, thereby maintaining patency in the small airways. Recent reports demonstrated that surfactant dysfunction develops in experimental asthma in immunized guinea pigs. However, there are few reports concerning surfactant and lung function in an experimental asthma model. OBJECTIVE: To examine whether inhaled surfactant improves lung mechanics in antigen-induced bronchoconstriction in guinea pigs. METHOD: We developed a passively immunized guinea pig model for allergic bronchoconstriction induced by antigen inhalation. Using this model, we investigated the effect of inhaled exogenous surfactant, surfactant TA, on the airway opening pressure (Pao) after antigen challenge. RESULTS: Aerosol antigen challenge produced a gradual and long-lasting increase in Pao. Twenty minutes after antigen challenge, aerosolized surfactant TA, 20 mg/ml, was inhaled for 90 s, and it significantly reduced the Pao by 32.8% in 12 min, while a 10.2% reduction was observed in a control group in the same period. When surfactant TA was administered by 90-s inhalation before antigen challenge, it inhibited the Pao increase in a dose-dependent manner: mean inhibitory rates of Pao were 33.6% in surfactant TA 10 mg/ml and 61.9% in surfactant TA 20 mg/ml, respectively. CONCLUSION: Inhaled surfactant showed preventive and recovery effects on antigeninduced bronchoconstriction in an immunized guinea pig model.

Administration, Inhalation↗

PubMed1999

Compositional, structural, and functional alterations in pulmonary surfactant in surgical patients after the early onset of systemic inflammatory response syndrome or sepsis.

OBJECTIVES: Sepsis is one of the most important predisposing factors for the development of the acute respiratory distress syndrome (ARDS). Alterations of pulmonary surfactant contribute in the pathogenesis of ARDS. However, little is known about surfactant in patients with less severe grades of lung injury related to sepsis or systemic inflammatory response syndrome (SIRS). Therefore, the purpose of this study was to characterize endogenous surfactant in surgical intensive care patients with sepsis or SIRS. DESIGN: Prospective, observational study. SETTING: University-affiliated, interdisciplinary intensive care unit. PATIENTS: Eleven patients after major surgery with SIRS or sepsis included within 12 hrs of onset and 11 controls without infection or lung disease. INTERVENTIONS: Operating room and standard intensive care unit management. MEASUREMENTS AND MAIN RESULTS: Four serial bronchoalveolar lavage samples (BAL) were recovered over 7 days from the patients and single BAL samples were obtained from controls. BAL cells, total protein, surfactant-associated protein A (SP-A), surfactant alveolar transition forms, and surface activity were analyzed. Two of 11 patients met criteria for acute lung injury and six of the 11 patients met ARDS consensus conference criteria but acute lung injury or ARDS was not persistent. The mean Pao2/F(IO)2 for the patients over 7 days was 253.2+/-15.1 (SEM) and Murray's lung injury score was 1.12+/-0.12, indicating mild-to-moderate lung injury. BAL neutrophil counts were increased (p< .01), and the ratio of poorly functioning light aggregate surfactant to superiorly functioning heavy aggregate surfactant was increased compared with controls (0.32+/-0.06 vs. 0.09+/-0.01, p < .05). SP-A was decreased (1.9+/-0.4 vs. 3.5+/-0.6 microg/mL of BAL, p< .05) and there were increases in the ratios of phospholipid to SP-A (p < .05), protein to SP.A (p < .01), and protein to phospholipid (p < .05). The surface tension-lowering ability of purified heavy aggregate surfactant was significantly impaired (15.6+/-1.6 vs. 2.8+/-0.6 milliNewtons/m, p< .05). CONCLUSIONS: These observations show that surgical patients with SIRS or sepsis who have mild-to-moderate lung injury develop surfactant dysfunction detectable within 7 days of onset. We propose, therefore, that therapeutic strategies to modulate these severe surfactant abnormalities should be considered, as these strategies may have the potential to reduce lung injury, which is associated with a high mortality in sepsis.

APACHE↗

PubMed2000

Interleukin-5-mediated allergic airway inflammation inhibits the human surfactant protein C promoter in transgenic mice.

Allergen challenge in the lung of humans and animals is associated with surfactant dysfunction, but the mechanism of this effect has not been established. By using a murine model of asthma we now report the effect of allergen-induced airway inflammation on the expression of transgenes regulated by the human surfactant protein (hSP)-C promoter. The hSP-C 3.7-kilobase pair promoter was used to direct the expression of eotaxin, an eosinophil-selective chemokine, into the lungs of several transgenic lines. As expected, the transgenic mice expressed increased amounts of eotaxin mRNA and protein compared with wild-type mice. Surprisingly, following allergen challenge, there was a marked down-regulation of transgene mRNA in three independent transgenic lines. The down-regulation was in contrast to other related proteins such as endogenous eotaxin and surfactant protein D levels, which were both increased following allergen challenge. Consistent with specific down-regulation of the eotaxin transgene, there was no increase in pulmonary eosinophil levels in the transgenic mice above that found in wild-type mice. Analysis of hSP-C transgenic mice with distinct reporter genes and 3'-untranslated regions revealed that allergen challenge was directly affecting the hSP-C promoter. We hypothesized that allergen-induced down-regulation of the hSP-C promoter was related to the eosinophilic inflammation. To test this, we blocked eosinophilic inflammation in the lungs by treating mice with neutralizing antiserum against interleukin-5. Interestingly, this treatment also blocked allergen-induced inhibition of the hSP-C promoter. These results establish that allergic airway inflammation is associated with up-regulation of the surfactant proteins primarily involved in immunity, whereas down-regulation of the surfactant protein primarily involved in maintaining airway patency. Furthermore, the marked down-regulation of the hSP-C promoter is interleukin-5-dependent, implying a critical role for eosinophilic inflammation. These results suggest that alterations in surfactant protein levels may contribute to immune and airway dysfunction in asthma.

3' Untranslated Regions↗

PubMed1998

Surfactant inactivation and surfactant therapy in acute respiratory distress syndrome (ARDS).

Surfactant dysfunction constitutes an important element in the complex pathophysiology of acute respiratory distress syndrome (ARDS). In this disease, surfactant may become inactivated by plasma proteins leaking into the airspaces as a consequence of increased alveolar permeability. In addition, surfactant proteins may become degraded by proteolytic enzymes or free oxygen radicals released by inflammatory cells recruited to the airspaces. Regardless of the mechanism involved, surfactant inactivation or degradation may be counterbalanced by increasing the pool of surfactant in the airspaces, i.e., by replacement therapy. Surfactant therapy has been tested with promising results in animal models of ARDS triggered by, e.g., lung lavage, hyperoxia or exposure to various toxic agents. In general, the response to surfactant treatment depends on the quality of the surfactant, timing of treatment in relation to the degree of lung injury, dosage and mode of administration. Encouraging results have been obtained with modified natural surfactants in clinical pilot studies on patients with ARDS, justifying further evaluation of this therapeutic approach in randomized controlled trials.

Animals↗

PubMed2005

Absence of heme oxygenase-1 expression in the lung parenchyma exacerbates endotoxin-induced acute lung injury and decreases surfactant protein-B levels.

Acute respiratory distress syndrome (ARDS) is a devastating disease process characterized by severe acute lung injury, inflammatory cell recruitment to the lung, upregulation of pro-inflammatory cytokines and increased oxidative stress. Epithelial cell injury, diffuse alveolar damage and surfactant dysfunction ensue leading to refractory hypoxemic respiratory failure. There are no specific effective therapies for ARDS and novel therapeutic approaches are desperately needed. In this study we assessed the role of the cytoprotective and anti-inflammatory enzyme heme oxygenase (HO)-1 in a model of nebulized endotoxin-induced acute lung injury. HO-1 null (HO-1(-/-)) mice exhibited severe physiologic lung dysfunction following lipopolysaccharide (LPS) nebulization, but had similar inflammatory responses as wild-type (WT) mice. However, a dramatic reduction in surfactant protein-B (SP-B) expression was observed in the lungs of LPS-treated HO-1(-/-) mice compared with similarly treated WT mice. Using reciprocal bone marrow transplantation (BMT) to generate HO-1-chimeric mice, we found that absence of HO-1 in the lung parenchyma, not in bone marrow-derived inflammatory cells, was responsible for enhanced SP-B downregulation and severe physiologic lung dysfunction. These findings have implications for our understanding of the pathophysiology of ARDS and may guide future therapeutic strategies.

Animals↗

PubMed1999

Treatment of meconium aspiration syndrome with surfactant lavage in an experimental rabbit model.

Meconium aspiration syndrome (MAS) is a frequent cause of respiratory distress in term infants. Recent reports suggested that surfactant dysfunction contributes to the pathophysiology of MAS. In the present study, we assessed the effect of three different concentrations of surfactant suspensions in the lavage fluid of a rabbit model of MAS. Young animals were given 5 mL/kg of a 20% slurry of human meconium into the endotracheal tube and were then mechanically ventilated. The animals were divided into four groups receiving lavage fluids with either saline or surfactant suspensions (2.5 mg/mL, 5 mg/mL, and 10 mg/mL). Lavage was performed an hour after meconium instillation with one of the four solutions at 10 mL/kg in three divided doses. After lavage, the total amount of meconium recovered was measured. The 10 mg/mL surfactant lavage group had the best improvement in gas exchange, whereas the saline group had no improvement. The amount of meconium recovered was the best in the 10 mg/mL surfactant group among the four groups studied. On histologic examination, alveolar inflammation was less evident in the surfactant lavage groups than in the saline lavage group. It was concluded that lavage with surfactant solution at a concentration of 10 mg/mL washed out meconium most effectively, and improved gas exchange and lung histology in the rabbit model of MAS more than saline lavage.

Analysis of Variance↗

PubMed2006

Morphological alterations of exogenous surfactant inhibited by meconium can be prevented by dextran.

BACKGROUND: Surfactant dysfunction due to inhibition is involved in the pathophysiology of meconium aspiration syndrome. Dextran addition has been shown to reverse exogenous surfactant inactivation by meconium, but the precise mechanisms and the morphological correlate of this effect are yet unknown. Morphological surfactant analysis by transmission electron microscopy (TEM) and stereology allows the differentiation of active (large aggregates = LA) and inactive (small aggregates = SA) subtypes. METHODS: To determine the in vitro effects of meconium and dextran addition on the morphology of a modified porcine natural surfactant (Curosurf), Curosurf samples were either incubated alone or together with meconium or with meconium and dextran, fixed and processed for TEM. Volume fractions of surfactant subtypes [lamellar body-like forms (LBL), multilamellar vesicles (MV), unilamellar vesicles (UV)] were determined stereologically. RESULTS: All preparations contained LBL and MV (corresponding to LA) as well as UV (corresponding to SA). The volume fraction of UV increased with addition of meconium and decreased with further addition of dextran. Correspondingly, the UV/(LBL+MV) ratio (resembling the SA/LA ratio) increased when meconium was added and decreased when dextran was added to the surfactant-meconium mixture. CONCLUSION: Meconium causes alterations in the ultrastructural composition of Curosurf that can be visualized and analyzed by TEM and stereology. These alterations resemble an increase in the SA/LA ratio and are paralleled by an increase in minimum surface tension. Dextran prevents these effects and may therefore be a useful additive to exogenous surfactant preparations to preserve their structural and functional integrity, thereby improving their resistance to inactivation.

Biological Products↗

PubMed1991

Inhibition of pulmonary surfactant function by meconium.

The pathophysiology of meconium aspiration is marked by lung hyperinflation because of airway obstruction, which is often followed by an acute pneumonitis with classic lung injury characteristics. Surfactant dysfunction may contribute to this latter pulmonary pathophysiology. We sought to determine to what extent meconium itself might contribute to a functional surfactant deficiency. Specimens of newborn infants' first meconium were collected and pooled. Serial dilutions of the meconium were then added to various concentrations of calf lung surfactant extract, a mixture with the surface properties of natural surfactant that is used clinically to treat neonatal respiratory distress syndrome, and the dynamic surface activity of these mixtures was studied with a pulsating bubble surfactometer. At surfactant concentrations of less than or equal to 1.5 mg/ml, even 6500-fold dilutions of meconium-inhibited surface tension lowering ability (10 +/- 2 mN/m vs 1 +/- 0.1 mN/m for controls, p less than 0.05). Moreover, this inhibitory activity resided in both the chloroform-soluble and the aqueous phases of meconium and appeared to be additive in nature. However, at sufficiently high concentrations of surfactant, even large amounts of meconium were unable to affect surface tension lowering properties. Thus meconium inhibits surfactant function in a manner that is dependent on the surfactant concentration, suggesting the possible utility of exogenous surfactant therapy in some cases of meconium aspiration.

Animals↗

PubMed1998

Aerosolized surfactant improves pulmonary function in endotoxin-induced lung injury.

Surfactant dysfunction is a primary pathophysiologic component in patients with adult respiratory distress syndrome (ARDS). In this study we tested the efficacy of aerosolized surfactant (Sf ) replacement in a severe lung injury model of endotoxin-induced ARDS. Twenty-one certified healthy pigs were anesthetized, surgically prepared for measurement of hemodynamic and lung function, then randomized into one of four groups: (1) control (n = 5), surgical instrumentation only; (2) lipopolysaccharide (LPS) (n = 6), infused with Escherichia coli LPS (100 microgram/kg) without positive end- expiratory pressure (PEEP) and ventilated with a nonhumidified gas mixture of 50% N2O and 50% O2; (3) LPS + PEEP (n = 4), infused with LPS, placed on PEEP (7.5 cm H2O), and ventilated with a humidified gas mixture; and (4) LPS + PEEP + Sf (n = 6), infused with LPS, placed on PEEP, and ventilated with aerosolized Sf (Infasurf, ONY, Inc.). All animals were studied for 6 h. Arterial PO2 significantly decreased in both the LPS and LPS + PEEP groups (LPS + PEEP = 74 +/- 19 mm Hg; LPS = 74 +/- 19 mm Hg, p < 0.05) while venous admixture (Q S/Q T) increased in these groups (LPS + PEEP = 43.3 +/- 3.9%; LPS = 47.7 +/- 11%, p < 0.05) as compared with the control group. PEEP + Sf reduced the fall in PO2 (142 +/- 20 mm Hg) and rise in Q S/Q T (15.1 +/- 3.6%) caused by LPS. Delayed induction of PEEP (2 h following LPS) did not significantly improve any parameter over the LPS group without PEEP in this ARDS model. LPS without PEEP (3.4 +/- 0.2 cells/6,400 micrometer2) caused a marked increase in the total number of sequestered leukocytes in the pulmonary parenchyma as compared with the control group (1.3 +/- 0.1 cells/6,400 micrometer2). LPS + PEEP + Sf (2.3 +/- 0.2 cells/6,400 micrometer2) significantly decreased while LPS + PEEP significantly increased (4.0 +/- 0.2 cells/6,400 micrometer2) the total number of sequestered leukocytes as compared with the LPS without PEEP group. In summary, aerosolized surfactant replacement decreased leukocyte sequestration and improved oxygenation in our porcine model of endotoxin-induced lung injury.

Aerosols↗

PubMed2003

Chlamydia pneumoniae affect surfactant trafficking and secretion due to changes of type II cell cytoskeleton.

Understanding the surfactant dysfunction by gram-negative bacteria pulmonary infection, the intracellular fate of Chlamydia pneumoniae (Cpn), its interaction with uptake, recycling, and secretion of surfactant and with the cytoskeleton of type II pneumocytes was investigated. Bacteria colocalized with surfactant protein (SP)-A-mediated endocytosed lipid and early endosomes (EEA1- and Rab5-positive) after 3 and 6 h of infection. No specific contact with late endosomes (Rab7- and M6PR-positive), lysosomal, or lamellar body markers (CD63, 3C9) was found after 12 h of infection. In Cpn-infected cells, SP-A-mediated lipid uptake was significantly increased. After SP-A-mediated lipid uptake followed by "re-secretion," 90% of the internalized lipid remained intracellularly. SP-A and lipid did strongly colocalize with early endosomes. Internalized SP-A cannot be resecreted rapidly to plasma membrane, and lipid is not transported toward late endosomes (Rab7- and M6PR-positive) or lamellar bodies (CD63- and 3C9-positive). These results indicate that increased surfactant internalization is caused by an inhibition in intracellular surfactant transport. Accumulation of SP-A-mediated lipid was associated with changes in beta-tubulin. Increases in surfactant secretion were associated with changes in F-actin. We postulate that Cpn infection of type II cells causes changes of the cytoskeleton, and that these effects are associated with alterations in intracellular transport and secretion of surfactant.

Actin Cytoskeleton↗

PubMed1998

In vitro inhibition of biophysical surface properties and change in ultrastructures of exogenous pulmonary surfactant by albumin or fibrinogen.

In order to observe the effects of serum albumin and fibrinogen on biophysical surface properties and the morphology of pulmonary surfactant in vitro, we measured the surface adsorption rate, dynamic minimum and maximum surface tension (min-, max-ST) by Pulsating Bubble Surfactometer, and demonstrated ultrastructures on a series of mixtures with varying concentrations of albumin or fibrinogen and Surfactant-TA. The albumin and fibrinogen significantly inhibited the adsorption rate and ST-lowering properties of surfactant through increasing STs of adsorption rate, min-ST, and max-ST. The characteristic morphology of the Surfactant-TA changed from lamellar rod-like structure with open ends into spherical structures with loss of their open ends by mixing with albumin or fibrinogen. These inhibitory effects of albumin and fibrinogen on surface properties of surfactant were dependent upon the increasing concentration of albumin or fibrinogen. We concluded that albumin and fibrinogen significantly altered surfactant function and its ultrastructural morphology in vitro. These findings support the concept that albumin and fibrinogen-induced surfactant dysfunction may play an important role in the pathophysiology of adult respiratory distress syndrome, and this adverse effect of albumin and fibrinogen on surfactant might be overcome by administration of large doses of exogenous surfactant.

Adsorption↗

PubMed2003

Inhibitory effects of surfactant protein A on surfactant phospholipid hydrolysis by secreted phospholipases A2.

Hydrolysis of surfactant phospholipids by secreted phospholipases A(2) (sPLA(2)) contributes to surfactant dysfunction in acute respiratory distress syndrome. The present study demonstrates that sPLA(2)-IIA, sPLA(2)-V, and sPLA(2)-X efficiently hydrolyze surfactant phospholipids in vitro. In contrast, sPLA(2)-IIC, -IID, -IIE, and -IIF have no effect. Since purified surfactant protein A (SP-A) has been shown to inhibit sPLA(2)-IIA activity, we investigated the in vitro effect of SP-A on the other active sPLA(2) and the consequences of sPLA(2)-IIA inhibition by SP-A on surfactant phospholipid hydrolysis. SP-A inhibits sPLA(2)-X activity, but fails to interfere with that of sPLA(2)-V. Moreover, in vitro inhibition of sPLA(2)-IIA-induces surfactant phospholipid hydrolysis correlates with the concentration of SP-A in surfactant. Intratracheal administration of sPLA(2)-IIA to mice causes hydrolysis of surfactant phosphatidylglycerol. Interestingly, such hydrolysis is significantly higher for SP-A gene-targeted mice, showing the in vivo inhibitory effect of SP-A on sPLA(2)-IIA activity. Administration of sPLA(2)-IIA also induces respiratory distress, which is more pronounced in SP-A gene-targeted mice than in wild-type mice. We conclude that SP-A inhibits sPLA(2) activity, which may play a protective role by maintaining surfactant integrity during lung injury.

Airway Resistance↗

PubMed1998

Hydrolysis of surfactant-associated phosphatidylcholine by mammalian secretory phospholipases A2.

Hydrolysis of surfactant-associated phospholipids by secretory phospholipases A2 is an important potential mechanism for surfactant dysfunction in inflammatory lung diseases. In these conditions, airway secretory phospholipase A2 (sPLA2) activity is increased, but the type of sPLA2 and its impact on surfactant function are not well understood. We examined in vitro the effect of multiple secretory phospholipases A2 on surfactant, including their ability to 1) release free fatty acids, 2) release lysophospholipids, and 3) increase the minimum surface tension (gammamin) on a pulsating bubble surfactometer. Natural porcine surfactant and Survanta were exposed to mammalian group I (recombinant porcine pancreatic) and group II (recombinant human) secretory phospholipases A2. Our results demonstrate that mammalian group I sPLA2 hydrolyzes phosphatidylcholine (PC), producing free fatty acids and lysophosphatidylcholine, and increases gammamin. In contrast, mammalian group II sPLA2 demonstrates limited hydrolysis of PC and does not increase gammamin. Group I and group II secretory phospholipases A2 from snake venom hydrolyze PC and inhibit surfactant function. In summary, mammalian secretory phospholipases A2 from groups I and II differ significantly from each other and from snake venom in their ability to hydrolyze surfactant-associated PC.

Animals↗

PubMed1996

Pulmonary surfactant given prophylactically alleviates an asthma attack in guinea-pigs.

BACKGROUND: Previous studies have indicated that the increased airway resistance that develops in asthma may partly be due to a surfactant dysfunction. If so, it might be possible to alleviate the acute signs following an allergen challenge by prophylactically instilling into the airways a well functioning pulmonary surfactant. OBJECTIVE: The study was planned and enacted to test the above hypothesis. METHODS: The lung function (airway resistance, tidal volume, minute ventilation, and dynamic compliance) of 22 immunized guinea-pigs was studied for 30 min following a challenge. Ten of the animals had received a tracheal instillation of 0.5 mL calf lung surfactant extract (CLSE, 35 mg/mL) prior to the challenge. RESULTS: The animals receiving the dose of 17.5 mg surfactant were less affected by the challenge than were the controls. Only one of them died following the challenge, whereas four of the 12 controls succumbed. Lung function was significantly less affected among the nine surviving animals treated with surfactant prior to the challenge than among the eight surviving controls (P < 0.01) and also their blood gases (pCO2 and pO2) were less influenced (P < 0.05). CONCLUSION: The study indicated that the symptoms developing after a challenge, which to some extent simulate those of asthma, can be alleviated by a prophylactic airway instillation of pulmonary surfactant.

Animals↗

PubMed2004

Mechanical ventilation effect on surfactant content, function, and lung compliance in the newborn rat.

Studies of ventilator-associated lung injury in adult experimental animal models have documented that high tidal volume (TV) results in lung injury characterized by impaired compliance and dysfunctional surfactant. Yet, there is evidence that, in neonates, ventilation with a higher than physiologic TV leads to improved lung compliance. The purpose of our study was to evaluate how lung compliance and surfactant was altered by high TV ventilation in the neonate. We utilized a new model (mechanically air-ventilated newborn rats, 4-8 d old), and used 40 or 10 mL/kg TV strategies. Age-matched nonventilated animals served as controls. In all animals, dynamic compliance progressively increased after initiation of mechanical ventilation and was significantly greater than basal values after 60 min (p < 0.01). Lung lavage total surfactant with both TV strategies (p < 0.05) and the large aggregate fraction (only in TV = 40 mL/kg; p < 0.01) were significantly increased by 60 min of mechanical ventilation, compared with control animals. Ventilation with 40 mL/kg TV for 60 min adversely affected the lung surfactant surface-tension lowering properties (p < 0.01). After 180 min of ventilation with 40 mL/kg TV, the lung total surfactant content and dynamic compliance values were no longer distinct from the nonventilated animals' values. We conclude that, in the newborn rat, mechanical ventilation with a higher than physiologic TV increases alveolar surfactant content and, over time, alters its biophysical properties, thus promoting an initial but transient improvement in lung compliance.

Animals↗