Pulmonary surfactant-associated protein SP-B has little effect on acyl chains in dipalmitoylphosphatidylcholine dispersions

Morrow, Michael R.; Pérez‐Gil, Jesús; Simatos, G.; Boland, Carl; Stewart, June; Absolom, D. R.; Sarin, Viren; Keough, K. M. W.

doi:10.1021/bi00067a032

Cited by 71 publications

(74 citation statements)

References 28 publications

(24 reference statements)

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“…SP-B can order the head-group region of lipid bilayers and increase the gel-to-liquid crystal transition temperatures of fluid phospholipids (1,2,30,53,54). SP-B also broadens phase transition width, indicating an ability to disrupt or reduce order in at least a portion of the bilayer (1,2,23,24,30,43). The extensive molecular biophysical interactions between SP-B and phospholipids support a crucial role for this apoprotein in surfactant biophysical function consistent with the activity findings here.…”

Section: Discussionsupporting

confidence: 82%

“…Due to its overall amphipathic structure, SP-B likely occupies a relatively peripheral position in phospholipid bilayers where it can interact with both head groups and hydrophobic chains (1,10,40,42,43,53). SP-B can order the head-group region of lipid bilayers and increase the gel-to-liquid crystal transition temperatures of fluid phospholipids (1,2,30,53,54). SP-B also broadens phase transition width, indicating an ability to disrupt or reduce order in at least a portion of the bilayer (1,2,23,24,30,43).…”

Section: Discussionmentioning

confidence: 99%

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Content-dependent activity of lung surfactant protein B in mixtures with lipids

Wang

Baatz

Holm

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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The content-dependent activity of surfactant protein (SP)-B was studied in mixtures with dipalmitoyl phosphatidylcholine (DPPC), synthetic lipids (SL), and purified phospholipids (PPL) from calf lung surfactant extract (CLSE). At fixed SP-B content, adsorption and dynamic surface tension lowering were ordered as PPL/SP-B ≈ SL/SP-B > DPPC/SP-B. All mixtures were similar in having increased surface activity as SP-B content was incrementally raised from 0.05 to 0.75% by weight. SP-B had small but measurable effects on interfacial properties even at very low levels ≤0.1% by weight. PPL/SP-B (0.75%) had the highest adsorption and dynamic surface activity, approaching the behavior of CLSE. All mixtures containing 0.75% SP-B reached minimum surface tensions <1 mN/m in pulsating bubble studies at low phospholipid concentration (1 mg/ml). Mixtures of PPL or SL with SP-B (0.5%) also had minimum surface tensions <1 mN/m at 1 mg/ml, whereas DPPC/SP-B (0.5%) reached <1 mN/m at 2.5 mg/ml. Physiological activity also was strongly dependent on SP-B content. The ability of instilled SL/SP-B mixtures to improve surfactant-deficient pressure-volume mechanics in excised lavaged rat lungs increased as SP-B content was raised from 0.1 to 0.75% by weight. This study emphasizes the crucial functional activity of SP-B in lung surfactants. Significant differences in SP-B content between exogenous surfactants used to treat respiratory disease could be associated with substantial activity variations.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Content-dependent activity of lung surfactant protein B in mixtures with lipids

Wang

Baatz

Holm

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…This was concluded from the facts that the number of bands in the y, (CH,) progression are conserved for the SP-B/lipid spectra, indicating that the lipid acyl chains retain an all-trans orientation also in the presence of SP-B and that the dichroic ratio corresponding to the y,(CH,) vibration is practically unchanged upon addition of SP-B (Vandenbussche et al, 1992a). Likewise, only slight perturbations of the packing of the acyl chains of Pam,GroPCho in the presence of synthetic human SP-B was reported by *H NMR (Morrow et al, 1993a).…”

Section: Protein-lipid Interactions In Surfactantmentioning

confidence: 94%

“…The secondary structure of SP-B has been determined in different environments, including organic solvents (Ptrez-Gil et al, 1993;Morrow et al, 1993a), detergent micelles (Andersson et al, 1995a), lipid bilayers (Vandenbussche et al, 1992a;Baatz et al, 1992;Perez-Gil et al, 1993;Morrow et al, 1993a) and lipid monolayers (Oosterlaken-Dijksterhuis et al, 1991 a). Largely independent of environment and method of analysis used [CD or Fourier-transform infrared (FTIR) spectroscopy], SP-B exhibits an overall content of 27-45% a-helical structure while the determined content of P-sheet structures ranges over 1-42% (see Vandenbussche et al, 1995).…”

Section: Structures Of the Hydrophobic Proteins Sp-b And Sp-cmentioning

confidence: 99%

Molecular Structures and Interactions of Pulmonary Surfactant Components

Johansson

Curstedt

1997

European Journal of Biochemistry

272

217

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The dominating functional property of pulmonary surfactant is to reduce the surface tension at the alveolar aidliquid interface, and thereby prevent the lungs from collapsing at the end of expiration. In addition, the system exhibits host-defense properties. Insufficient amounts of pulmonary surfactant in premature infants causes respiratory distress syndrome, a serious threat which nowadays can be effectively treated by airway instillation of surfactant preparations. Surfactant is a mixture of many molecular species, mainly phospholipids and specific proteins, surfactant protein A (SP-A), SP-B, SP-C and SP-D. SP-A and SP-D are water-soluble and belong to the collectins, a family of large multimeric proteins which structurally exhibit collagenousAectin hybrid properties and functionally are Caz+-dependent carbohydrate binding proteins involved in innate host-defence functions. SP-A and SP-D also bind lipids and SP-A is involved in organization of alveolar surfactant phospholipids. SP-B belongs to another family of proteins, which includes also lipid-interacting polypeptides with antibacterial and lytic properties. SP-B is a 17.4-kDa homodimer and each subunit contains three intrachain disulphides and has been proposed to contain four amphipathic helices oriented pairwise in an antiparallel fashion. SP-A, SP-B and SP-D all have been detected also in the gastrointestinal tract. SP-C, in contrast, appears to be a unique protein with extreme structural and stability properties and to exist exclusively in the lungs. SP-C is a lipopeptide containing covalently linked palmitoyl chains and is folded into a 3.7-nm a-helix with a central 2.3-nm all-aliphatic part, making it perfectly suited to interact in a transmembranous way with a fluid bilayer composed of dipalmitoylglycerophosphocholine, the main component of surfactant. Homozygous genetic deficiency of proSP-B causes lethal respiratory distress soon after birth and is associated with aberrant processing of the precursor of SP-C. This review focuses on the chemical composition, structures and interactions of the pulmonary surfactant, in particular the associated proteins.

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“…However, a molecular structure of SP-B, the only member of the saposin family that is permanently associated with membranes, is still not available despite the fact that some molecular modelling efforts have been reported [69,70]. Numerous studies have approached the analysis of structural determinants in SP-B by means of indirect techniques such as circular dichroism [71,72] [73], fluorescence [74] or infrared spectroscopies [75,76], or electron spin resonance (ESR) [77]. The protein structure is dominated by a 40-50% "-helix, predicted to be in the form of amphipathic helical segments with well-defined polar and non-polar faces.…”

Section: Structure-function Relationships Of Sp-bmentioning

confidence: 99%

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

Mingarro¹,

Lukovic²,

Vilar³

et al. 2008

CMC

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Pulmonary surfactant is a lipid-protein complex that coats the interior of the alveoli and enables the lungs to function properly. Upon its synthesis, lung surfactant adsorbs at the interface between the air and the hypophase, a capillary aqueous layer covering the alveoli. By lowering and modulating surface tension during breathing, lung surfactant reduces respiratory work of expansion, and stabilises alveoli against collapse during expiration.Pulmonary surfactant deficiency, or dysfunction, contributes to several respiratory pathologies, such as infant respiratory distress syndrome (IRDS) in premature neonates, and acute respiratory distress syndrome (ARDS) in children and adults. The main clinical exogenous surfactants currently in use to treat some of these pathologies are essentially organic extracts obtained from animal lungs. Although very efficient, natural surfactants bear serious defects: i) they could vary in composition from batch to batch; ii) their production involves relatively high costs, and sources are limited; and iii) they carry a potential risk of transmission of animal infectious agents and the possibility of immunological reaction. All these caveats justify the necessity for a highly controlled synthetic material.In the present review the efforts aimed at new surfactant development, including the modification of existing exogenous surfactants by adding molecules that can enhance their activity, and the progress achieved in the production of completely new preparations, are discussed. Pulmonary surfactant function and dysfunctionThe respiratory surface of lungs constitutes the largest area of the human body exposed to the environment. Efficient gas exchange requires a large enough surface to be continuously exposed to air while minimising the barriers for oxygen and carbon dioxide to diffuse between air and the blood compartment [1]. At the same time, a selection of combined defence mechanisms is required to help keep such an essentially exposed area sterile of potential pathogenic microorganisms. Pulmonary surfactant, a lipid-protein complex produced by the alveolar epithelium of lungs, has been optimised to coordinate two main activities through natural evolution. On the one hand, it stabilises the respiratory surface against physical forces, therefore minimising the work required to maintain the large respiratory surface open to air [2][3][4]. On the other hand, pulmonary surfactant contains elements responsible for establishing a primary innate antipathogenic barrier, essential to ensure an intrinsically low pathogen load in the absence of induced defence mechanisms [5]. Extensive research in the last few decades has revealed some of the molecular mechanisms involved in pulmonary surfactant action. However, the manner in which both the biophysical and defence activities are intermingled and coordinately modulated in the alveolar spaces is now only beginning to be envisioned.Pulmonary surfactant is composed of approximately 90% lipids and 8-10% proteins, although only around 5% ...

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Pulmonary surfactant-associated protein SP-B has little effect on acyl chains in dipalmitoylphosphatidylcholine dispersions

Cited by 71 publications

References 28 publications

Content-dependent activity of lung surfactant protein B in mixtures with lipids

Content-dependent activity of lung surfactant protein B in mixtures with lipids

Molecular Structures and Interactions of Pulmonary Surfactant Components

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

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