Altered Phospholipid Composition and Aggregate Structure of Lung Surfactant Is Associated with Impaired Lung Function in Young Children with Respiratory Infections

Mander, Ann; Hewer, Simon C Langton; Bernhard, Wolfgang; Warner, John O.; Postle, Anthony D.

doi:10.1165/rcmb.4746

Cited by 57 publications

(51 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The high percentage of phospholipid in secreted material was in agreement with other studies of secretion from lungs in vivo (3) and with recent studies with adult type II alveolar epithelial cells in vitro (19,20). The ratios of SP-A and SP-B to phospholipid secreted from these cells were similar to those in tracheal aspirate samples from premature infants.…”

Section: Characterization Of Fetal Alveolar Epithelial Cells Differensupporting

confidence: 90%

Lipidomics of cellular and secreted phospholipids from differentiated human fetal type II alveolar epithelial cells

Postle

Gonzales

Bernhard

et al. 2006

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

Maturation of fetal alveolar type II epithelial cells in utero is characterized by specific changes to lung surfactant phospholipids. Here, we quantified the effects of hormonal differentiation in vitro on the molecular specificity of cellular and secreted phospholipids from human fetal type II epithelial cells using electrospray ionization mass spectrometry. Differentiation, assessed by morphology and changes in gene expression, was accompanied by restricted and specific modifications to cell phospholipids, principally enrichments of shorter chain species of phosphatidylcholine (PC) and phosphatidylinositol, that were not observed in fetal lung fibroblasts. Treatment of differentiated epithelial cells with secretagogues stimulated the secretion of functional surfactant-containing surfactant proteins B and C (SP-B and SP-C). Secreted material was further enriched in this same set of phospholipid species but was characterized by increased contents of short-chain monounsaturated and disaturated species other than dipalmitoyl PC (PC16:0/16:0), principally palmitoylmyristoyl PC (PC16:0/14:0) and palmitoylpalmitoleoyl PC (PC16:0/16:1). Mixtures of these PC molecular species, phosphatidylglycerol, and SP-B and SP-C were functionally active and rapidly generated low surface tension on compression in a pulsating bubble surfactometer. These results suggest that hormonally differentiated human fetal type II cells do not select the molecular composition of surfactant phospholipid on the basis of saturation but, more likely, on the basis of acyl chain length. Although all differentiated cells in vivo maintain a specific membrane phospholipid composition optimized for their individual functions, little is known about the precise functional role of any individual phospholipid molecular species. An exception perhaps is the role of phosphatidylcholine (PC) molecular species in the action of pulmonary surfactant within the lung alveoli and airways. The function of dipalmitoyl PC (PC16:0/16:0, characterized by the presence of two saturated fatty acids) as the major surfaceactive agent of lung surfactant is arguably the best-defined role for any individual phospholipid species. Pulmonary surfactant is secreted from the type II epithelial cell of the alveolus, and the ontogeny of both surfactant and the type II cell is well defined. From z22 weeks of human gestation, type II cells progressively acquire cytoplasmic lamellar bodies, which are the sites for storage of surfactant lipids and proteins in anticipation of postnatal life. The fractional content of PC16:0/16:0 in fetal lung increases over this time period in utero, from z25 mol% total PC at 15 weeks of gestation to 45 mol% at term birth (1).Intriguingly, comparative analysis from a wide range of mammals and marsupials indicates that PC16:0/16:0 is not always the major PC component of lung surfactant (2). Other short-chain species, typically palmitoylmyristoyl PC (PC16:0/14:0) and palmitoylpalmitoleoyl PC (PC16:0/ 16:1), predominate in a number of fast-breathing anim...

show abstract

Section: Characterization Of Fetal Alveolar Epithelial Cells Differensupporting

confidence: 90%

Lipidomics of cellular and secreted phospholipids from differentiated human fetal type II alveolar epithelial cells

Postle

Gonzales

Bernhard

et al. 2006

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…In contrast to the situation in severely injured lungs, the relatively mild lung injury observed in these spontaneously breathing septic animals was associated with no changes in LA pool sizes but a decrease in SA. This resulted in an increased percentage of LA in these spontaneously breathing animals, a finding also reported in a human study evaluating spontaneously breathing children with respiratory infections [12]. The current authors speculate that these changes in the endogenous surfactant system represent a compensatory response of the host to the initial insult.…”

Section: Discussionsupporting

confidence: 82%

“…Although earlier interventions would seem appropriate, a better understanding of surfactant alterations at this stage of the disease is required to justify this approach. Recent studies have shown that changes in the alveolar surfactant subfractions occur in animals and humans with less severe lung injury, while spontaneously breathing [10][11][12].…”

mentioning

confidence: 99%

Mechanisms responsible for surfactant changes in sepsis-induced lung injury

Huang

McCaig²,

Veldhuizen³

et al. 2005

European Respiratory Journal

View full text Add to dashboard Cite

Pulmonary surfactant is altered in sepsis, and these changes contribute to the predisposition of septic lungs to subsequent insults, ultimately leading to acute lung injury. Specifically, the total amount of surfactant is lower in sepsis, mainly due to decreased small aggregate (SA) surfactant pools. The amount of large aggregate (LA) surfactant is not altered.To evaluate the mechanisms responsible for these alterations, trace doses of tritium-labelled dipalmitoylphosphatidylcholine ( 3 H-DPPC)-labelled LA were instilled intratracheally into adult rats 20 hrs after caecal ligation and perforation (CLP) or sham surgery. Animals were sacrificed at 0, 1 and 4 h after instillation and recovery of 3 H-DPPC in alveolar macrophages (AM), LA and SA was measured. In separate in vitro experiments, AM isolated from CLP/sham rats were incubated with LA or SA isolated from normal animals to evaluate the uptake of these aggregates into the AM. Results showed increased surfactant radioactivity associated with AM of CLP animals compared with sham animals both in vivo and in vitro. In addition, more 3 H-DPPC label remained in LA forms in the CLP animals in vivo compared with sham.These findings indicate that differences in surfactant aggregate uptake and large aggregate conversion occur in septic lungs, resulting in changes in surfactant pools.

show abstract

“…Recently, elevated minimum surface tension values were found in surfactant isolated from children with cystic fibrosis and with pneumonia; surfactant proteins were not examined in that study (33). Adults with acute respiratory distress syndrome have low concentrations of SP-A and SP-B both before and during their lung disease, and minimum surface tension is elevated (30,44,45).…”

mentioning

confidence: 93%

“…None of the observed changes in phospholipid composition is likely to affect surfactant function, particularly in view of unchanged phosphatidylcholine content. The concentration of saturated phosphatidylcholine in surfactant is reduced in both pneumonia and adult acute respiratory distress syndrome (20,33). Because of the limited amount of surfactant pellet from each TA collection, we performed the measurements of phospholipid composition on pooled residual samples and were not able to assess either saturated phosphatidylcholine or molecular species of phosphatidylcholine.…”

mentioning

confidence: 99%

Dysfunction of Pulmonary Surfactant in Chronically Ventilated Premature Infants

Merrill¹,

Ballard²,

Cnaan³

et al. 2004

Pediatr Res

View full text Add to dashboard Cite

Infants of Ͻ30 wk gestation often require respiratory support for several weeks and may develop bronchopulmonary dysplasia (BPD), which is associated with long-term pulmonary disability or death in severe cases. To examine the status of surfactant in infants at high risk for BPD, this prospective study analyzed 247 tracheal aspirate samples from 68 infants of 23-30 wk gestation who remained intubated for 7-84 d. Seventy-five percent of the infants had one or more surfactant samples with abnormal function (minimum surface tension 5.1-21.7 mN/m by pulsating bubble surfactometer), which were temporally associated with episodes of infection (p ϭ 0.01) and respiratory deterioration (p ϭ 0.005). Comparing normal and abnormal surfactant samples, there were no differences in amount of surfactant phospholipid, normalized to total protein that was recovered from tracheal aspirate, or in relative content of phosphatidylcholine and phosphatidylglycerol. Contents of surfactant proteins (SP) A, B, and C, measured in the surfactant pellet by immunoassay, were reduced by 50%, 80%, and 72%, respectively, in samples with abnormal surface tension (p Յ 0.001). On multivariable analysis of all samples, SP-B content (r ϭ Ϫ0.58, p Ͻ 0.0001) and SP-C content (r ϭ Ϫ0.32, p Ͻ 0.001) were correlated with surfactant function. We conclude that most premature infants requiring continued respiratory support after 7 d of age experience transient episodes of dysfunctional surfactant that are associated with a deficiency of SP-B and SP-C. Infants born prematurely, particularly those of Յ30 wk gestation, are at high risk for lung disease. Although the incidence and severity of respiratory distress syndrome has been reduced with antenatal corticosteroid therapy, which hastens lung development, and postnatal replacement surfactant treatment, newborn respiratory distress remains a frequent occurrence in very low birth weight infants and a requirement for respiratory support often continues for many weeks (1, 2). The clinical pattern after the first week of life frequently includes episodes of respiratory deterioration necessitating increased inspired oxygen or ventilatory support (3). In some infants, lung disease progresses to BPD, which is defined as a continuing requirement for supplemental oxygen and/or positive pressure ventilatory support at 36 wk postmenstrual age (4). BPD occurs in approximately 30% of infants with birth weights Ͻ1000 g and is associated with long-term pulmonary and/or neurodevelopmental disability or death in severe cases (4, 5). The etiology of this progressive respiratory insufficiency is likely multifactorial, including oxygen toxicity, volutrauma associated with mechanical ventilation, infection, patent ductus arteriosus, and inflammation, and results in arrest of alveolar development and interstitial fibrosis (4).Pulmonary surfactant is a mixture of lipids and proteins produced by alveolar type II cells. The major phospholipid component, saturated phosphatidylcholine, forms a highly surface-active film in lung alveoli ...

show abstract

Altered Phospholipid Composition and Aggregate Structure of Lung Surfactant Is Associated with Impaired Lung Function in Young Children with Respiratory Infections

Cited by 57 publications

References 28 publications

Lipidomics of cellular and secreted phospholipids from differentiated human fetal type II alveolar epithelial cells

Lipidomics of cellular and secreted phospholipids from differentiated human fetal type II alveolar epithelial cells

Mechanisms responsible for surfactant changes in sepsis-induced lung injury

Dysfunction of Pulmonary Surfactant in Chronically Ventilated Premature Infants

Contact Info

Product

Resources

About