Surfactant protein D influences surfactant ultrastructure and uptake by alveolar type II cells

Ikegami, Machiko; Na, Cheng-Lun; Korfhagen, Thomas R.; Whitsett, Jeffrey A.

doi:10.1152/ajplung.00142.2004

Cited by 81 publications

(81 citation statements)

References 38 publications

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“…The remaining small amount of SP-D associates with surfactant lipid and influences surfactant ultrastructure, at least in part, by its phosphatidylinositol-dependent lytic activity on phospholipid membranes, which is critical for surfactant homeostasis (10). In SP-D-deficient mice, the abnormally large surfactant forms are inefficiently taken up by type II cells, resulting in a threefold increase in the surfactant pool size (47,48). Survanta is a lipid extract of minced bovine lung, supplemented with dipalmitoyl-phosphatidylcholine, palmitic acid, and tripalmitin to favorably alter in vitro surface properties.…”

Section: Discussionmentioning

confidence: 99%

Surfactant Protein-D Inhibits Lung Inflammation Caused by Ventilation in Premature Newborn Lambs

Sato¹,

Whitsett²,

Scheule³

et al. 2010

Am J Respir Crit Care Med

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Rationale: Premature newborns frequently require manual ventilation for resuscitation during which lung injury occurs. Although surfactant protein (SP)-D regulates pulmonary inflammation, SP-D levels are low in the preterm lung. Commercial surfactants for treatment of respiratory distress syndrome do not contain SP-D. Objectives: To determine whether addition of recombinant human SP-D (rhSP-D) to commercial surfactant influences lung inflammation in ventilated premature newborn lambs. Methods: Prematurely delivered lambs (130 d gestation age) were resuscitated with 100% O 2 and peak inspiratory pressure 40 cm H 2 O for 20 minutes and then treated with Survanta or Survanta containing rhSP-D. Ventilation was then changed to regulate tidal volume at 8 to 9 ml/kg. At 5 hours of age lambs were killed for sample collection. Measurements and Main Results: Sequential blood gas and tidal volume were similar in lambs treated with or without rhSP-D, indicating that lung immaturity and ventilatory stress used to support premature lambs were comparable between the two groups. Ventilation caused pulmonary inflammation in lambs treated with surfactant alone. In contrast, surfactant containing rhSP-D decreased neutrophil numbers in bronchoalveolar lavage fluid and decreased neutrophil elastase activity in lung tissue. IL-8 mRNA and IL-8 protein were significantly decreased in the 1rhSP-D group lamb lungs, to 20% of those in controls. The addition of rhSP-D also rendered Survanta more resistant to plasma protein inhibition of surfactant function. Conclusions: Treatment with rhSP-D-containing surfactant inhibited lung inflammation and enhanced the resistance of surfactant to inhibition, supporting its potential usefulness for prevention of lung injury in the preterm newborn.

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Section: Discussionmentioning

confidence: 99%

Surfactant Protein-D Inhibits Lung Inflammation Caused by Ventilation in Premature Newborn Lambs

Sato¹,

Whitsett²,

Scheule³

et al. 2010

Am J Respir Crit Care Med

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“…Detailed analyses of surfactant metabolism in vivo in Sftpd 2/2 and Csf2 2/2 mice have shown that neither surfactant synthesis nor secretion was increased in these models (13,26,39). Rather, the defect was attributed to defective uptake and/or catabolism of surfactant by type II cells and alveolar macrophages due to altered surfactant ultrastructure (Sftpd 2/2 [40]) or impaired macrophage differentiation (Csf2 2/2 [41]). In contrast, SatPC synthesis and the SatPC alveolar-tissue SatPC index were significantly increased in 4-week-old Gpr116…”

Section: Surfactant In Gpr116mentioning

confidence: 99%

Orphan G Protein–Coupled Receptor GPR116 Regulates Pulmonary Surfactant Pool Size

Bridges

Ludwig

Müeller

et al. 2013

Am J Respir Cell Mol Biol

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Pulmonary surfactant levels within the alveoli are tightly regulated to maintain lung volumes and promote efficient gas exchange across the air/blood barrier. Quantitative and qualitative abnormalities in surfactant are associated with severe lung diseases in children and adults. Although the cellular and molecular mechanisms that control surfactant metabolism have been studied intensively, the critical molecular pathways that sense and regulate endogenous surfactant levels within the alveolus have not been identified and constitute a fundamental knowledge gap in the field. In this study, we demonstrate that expression of an orphan G protein-coupled receptor, GPR116, in the murine lung is developmentally regulated, reaching maximal levels 1 day after birth, and is highly expressed on the apical surface of alveolar type I and type II epithelial cells. To define the physiological role of GPR116 in vivo, mice with a targeted mutation of the Gpr116 locus, Gpr116 Dexon17, were generated. Gpr116 Dexon17 mice developed a profound accumulation of alveolar surfactant phospholipids at 4 weeks of age (12-fold) that was further increased at 20 weeks of age (30-fold). Surfactant accumulation in Gpr116Dexon17 mice was associated with increased saturated phosphatidylcholine synthesis at 4 weeks and the presence of enlarged, lipid-laden macrophages, neutrophilia, and alveolar destruction at 20 weeks. mRNA microarray analyses indicated that P2RY2, a purinergic receptor known to mediate surfactant secretion, was induced in Gpr116Dexon17 type II cells. Collectively, these data support the concept that GPR116 functions as a molecular sensor of alveolar surfactant lipid pool sizes by regulating surfactant secretion.Keywords: pulmonary surfactant; G protein-coupled receptors; GPR116; surfactant metabolism; alveolar epithelium Pulmonary surfactant is synthesized by alveolar type II cells and is primarily composed of phospholipids, which constitute 80% of the total mass. The remaining components include neutral lipids, the lipid-associated surfactant proteins SFTPB and SFTPC, and the hydrophilic surfactant proteins SFTPA and SFTPD (1, 2). Saturated phosphatidylcholine (SatPC) is uniquely enriched in surfactant and, in concert with SFTPB and SFTPC, is fundamentally required to reduce surface tension at the air/liquid interface within the alveolus (3, 4). After synthesis, the lipid and lipidassociated proteins SFTPB and SFTPC are routed to and stored in membrane-enclosed secretory organelles called lamellar bodies. Through constitutive pathways or upon stimulation by secretagogues (including purines [5,6], b-agonists [7][8][9], and adenosine [10, 11]) or mechanical stretch (12), lamellar bodies fuse with the plasma membrane and are exocytosed from type II cells into the alveolar space.The quantity of surfactant in the mammalian lung, referred to as surfactant pool size, increases dramatically during late gestation to facilitate the transition to air breathing at birth. In the fetal lung, the majority of surfactant is stored within type I...

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“…SP-D knockout mice however, accumulate phospholipids in the alveolar space leading to emphysematous changes (10) and increased susceptibility to infections (6). SP-D regulates the surfactant pool size by influencing the surfactant ultrastructure and its reuptake in type II cells (11). SP-D is a large, complex glycoprotein with monomeric structure forming trimers that cluster to form a quaternary cruciate structure (12).…”

Section: R Espiratory Distress Syndrome (Rds) Is a Main Contributormentioning

confidence: 99%

“…SP-D regulates the surfactant pool size by influencing the surfactant ultrastructure and its reuptake in type II cells (11). SP-D does not localize to lamellar bodies, but can, in absence of SP-A, form atypical but highly surface-active tubular aggregates by binding phosphatidylinositol, a component of mammalian surfactant that is increased in lung damage (29).…”

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confidence: 99%

Surfactant Protein D Levels in Umbilical Cord Blood and Capillary Blood of Premature Infants. The Influence of Perinatal Factors

et al. 2006

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Surfactant protein D (SP-D) is a collectin that plays an important role in the innate immune system and takes part in the surfactant homeostasis by regulating the surfactant pool size. The aims of this study were to investigate the values of SP-D in umbilical cord blood and capillary blood of premature infants and to relate the levels to perinatal conditions. A total of 254 premature infants were enrolled in the present study. Umbilical cord blood was drawn at the time of birth and capillary blood at regular intervals throughout the admission. The concentration of SP-D in umbilical cord blood and capillary blood was measured using ELISA technique. The median concentration of SP-D in umbilical cord blood was twice as high as in mature infants, 769 ng/mL (range 140 -2,551), with lowest values in infants with intrauterine growth retardation (IUGR) and rupture of membranes (ROM). The median concentration of SP-D in capillary blood day 1 was 1,466 ng/mL (range 410 -5,051 ng/mL), with lowest values in infants born with ROM and delivered vaginally. High SP-D levels in umbilical cord blood and capillary blood on day 1 were found to be more likely in infants in need for respiratory support or surfactant treatment and susceptibility to infections. We conclude that SP-D concentrations in umbilical cord blood and capillary blood in premature infants are twice as high as in mature infants and depend on several perinatal conditions. High SP-D levels in umbilical cord blood and capillary blood on day 1 were found to be related to increased risk of RDS and infections. R espiratory distress syndrome (RDS) is a main contributor to increased mortality and morbidity among premature infants. RDS is caused by lack of pulmonary surfactant leading to atelectasis and ventilation-perfusion mismatch of the lungs (1). Biochemically, pulmonary surfactant is a mixture of phospholipids and associated proteins which are synthesized, stored, secreted and recycled by type II cells in the airways (2). This mixture forms a monolayer at the air-liquid interface which lowers the surface tension, stabilizes alveoli and terminal airways at low lung volume and prevents alveolar collapse at the end of the expiration. Treatment with synthetic or naturally developed surfactant has been associated with a decline in the mortality of RDS among premature infants (3,4).Four specific surfactant proteins have been identified, called surfactant protein (SP) A-D. SP-B and SP-C have been characterized as hydrophobic polypeptides that enhance the adsorption of lipid to the surface of the alveoli (5), while SP-A and SP-D are hydrophilic and participate in the innate host defense immune system. SP-D binds to macrophages and neutrophils and promotes phagocytosis and killing of bacteria, fungi, and viruses (6). Polymorphism in the amino acid residue 11 of the SPD gene has been found to increase severity of respiratory syncytial virus infection and susceptibility to tuberculosis (7,8).SP-A and SP-B are instrumental in surfactant storage in lamellar bodies and i...

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Surfactant protein D influences surfactant ultrastructure and uptake by alveolar type II cells

Cited by 81 publications

References 38 publications

Surfactant Protein-D Inhibits Lung Inflammation Caused by Ventilation in Premature Newborn Lambs

Surfactant Protein-D Inhibits Lung Inflammation Caused by Ventilation in Premature Newborn Lambs

Orphan G Protein–Coupled Receptor GPR116 Regulates Pulmonary Surfactant Pool Size

Surfactant Protein D Levels in Umbilical Cord Blood and Capillary Blood of Premature Infants. The Influence of Perinatal Factors

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