Role of the palmitoylation of surfactant-associated protein C in surfactant film formation and stability

Qanbar, Riad; Cheng, Shuna; Possmayer, Fred; Schürch, Samuel

doi:10.1152/ajplung.1996.271.4.l572

Cited by 42 publications

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“…The resulting DPPC enrichment is considered necessary in order for the monolayer to achieve the low surface tensions required to stabilize the lung. Recently, a number of physicochemical studies have demonstrated that low surface tension can be achieved with smaller surface area reductions than would be predicted by the squeeze-out mechanism (43)(44)(45)(46). It has consequently been proposed that sorting or refining of surfactant lipids occurs during adsorption so as to generate a monolayer already enriched in DPPC (3-7, 37, 38).…”

Section: Discussionmentioning

confidence: 99%

“…Recent physicochemical measurements have demonstrated that surface area reductions required to attain surface tensions near 0 mN/m during initial film compression of adsorbed surfactant films can be lower than that predicted by the DPPC content of surfactant (37,(43)(44)(45)(46). These observations led to the proposal that the surface monolayer may become enriched in DPPC during adsorption (3-6, 37, 38).…”

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confidence: 99%

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Lipid compositional analysis of pulmonary surfactant monolayers and monolayer-associated reservoirs

Possmayer

2003

Journal of Lipid Research

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Pulmonary surfactant is a lipid:protein complex containing dipalmitoyl-phosphatidylcholine (DPPC) as the major component. Recent studies indicate adsorbed surfactant films consist of a surface monolayer and a monolayerassociated reservoir. It has been hypothesized that the monolayer and its functionally contiguous reservoir may be enriched in DPPC relative to bulk phase surfactant. We investigated the compositional relationship between the monolayer and its reservoir using paper-supported wet bridges to transfer films from adsorbing dishes to clean surfaces on spreading dishes. Spreading films appear to form monolayers in the spreading dishes. We employed bovine lipid ex- It is generally agreed that the alveolar surface is covered by a continuous thin layer of water that supports a surface active film of pulmonary surfactant (1, 2) [for review see (3-7)]. Through its ability to reduce the surface tension of this air-water interface, pulmonary surfactant stabilizes the terminal air spaces. Considerable evidence has accumulated indicating that surfactant films are composed of more than a single monolayer. Pattle (8) first proposed that the surfactant film overlying the alveolar lining layer consists of a monomolecular layer and underlying material that serves as a reservoir. Using electron microscopy, Weibel and Gil (9) observed the presence of lamellar layers of phospholipids with three to six repeating distances of 38-51 Å on the alveolar epithelial surface of rat lungs. Studies by Manabe (2) and, more recently, Bastacky et al. (1) using scanning electron microscopic studies indicate that the alveolar lining layer is continuous and its surface contains many lipidic structures. In vitro studies involving surface films adsorbed from surfactant dispersions have also provided evidence indicating the surface monolayer is accompanied by a functional continuous reservoir (10-13). Surfactant reservoirs that can provide phospholipids to the air-water interface during surface area expansion can also be created during film compression (14)(15)(16)(17) [as reviewed in refs. (18, 19)].Pulmonary surfactant consists of ‫ف‬ 90% lipids and ‫ف‬ 10% protein. The phospholipid composition of bovine pulmonary surfactant, which is representative of mammalian species, consists of ‫ف‬ 80% total phosphatidylcholines (PCs), 10-15% phosphatidylglycerol (PG), 2-3% each of phosphatidylethanolamine, phosphatidylinositol, and sphingomyelin, and 1-2% lyso-bis -phosphatidic acid (20). Dipalmitoylphosphatidylcholine (DPPC) and 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) are major molecular species, while dipalmitoylphosphatidylglycerol (DPPG) and 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG) are present at significant levels (20)(21)(22). Bovine pulmonary surfactant also contains ‫ف‬ 4% neutral lipids, of which ‫ف‬ 90% is cholesterol. Pulmonary surfactant proteins (SPs) consist of two small hydrophobic proteins, SP-B and SP-C, and two hydrophilic complex glycoproteins, .

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Lipid compositional analysis of pulmonary surfactant monolayers and monolayer-associated reservoirs

Possmayer

2003

Journal of Lipid Research

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“…Such actions Pure synthetic lipid mixtures had very low biophysical activities, but addition of 5% native porcine SP-C to the lipid mixtures would be expected to reduce the γ max values. Finally, the palmitoyl groups of native SP-C have recently been shown to be imincreased the spreading dramatically and all preparations reached a surface pressure higher than 40 mN/m within 10 min portant for full surface activity [47,48] and the lack of palmitoyl groups in SP-C(Leu) could contribute to its suboptimal proper- (Fig. 2).…”

Section: Discussionmentioning

confidence: 99%

Synthetic peptide‐containing surfactants

Nilsson

Gustafsson

Vandenbussche

et al. 1998

European Journal of Biochemistry

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Pulmonary surfactant contains two hydrophobic proteins, SP-B and SP-C. With the aim of identifying synthetic SP-B and SP-C substitutes for replacement therapy of respiratory distress syndromes, we have studied two transmembrane peptides and two amphipathic peptides that are located in the plane of a phospholipid bilayer. One amphipathic peptide was designed by changing the amino acid sequence, but not the composition or size, of the 21-residue peptide KL 4 . This peptide, designated KL 2.3 from its spacing of nonpolar and polar residues, exhibited similar A-helical content as KL 4 but was oriented along a phospholipid bilayer plane, in contrast to the transmembrane orientation of KL 4 in the same environment. The second amphipathic peptide analyzed was succinyl-LLEKLLEWLK-amide (WMAP10). KL 4 more efficiently accelerated the spreading of a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (Pam 2 -GroPCho)/phosphatidylglycerol (PtdGro)/palmitic acid (PamOH), 68:22:9 (by mass), at an air/water interface than did any of the amphipathic peptides. Similarly, KL 4 , but not KL 2.3 , when present in an interfacial monolayer composed of Pam 2GroPCho/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol, 7: 3 (by mass), increased lipid insertion from subphase vesicles.An SP-C analogue, SP-C(Leu), with all helical valyl residues in native SP-C replaced with Leu and the palmitoylcysteines at positions 5 and 6 replaced with Ser, but otherwise with essentially the same primary structure as the native peptide, was analyzed. SP-C(Leu) exhibited similar A-helical content as native SP-C and a transmembrane orientation and, in contrast to poly-valyl-containing synthetic peptides, it folds into a helical conformation after acid-induced denaturation. SP-C(Leu) accelerated the spreading of Pam 2 GroPCho/PtdGro/PamOH, 68:22:9 (by mass), almost identically to native SP-C, and lowered the surface tension during rapid cyclic film compressions in a pulsating bubble surfactometer to near zero and 43 mN/m at minimum and maximum bubble size, respectively. Airway instillation of 2% (by mass) SP-C(Leu) combined with Pam 2 GroPCho/PtdGro/PamOH in preterm rabbit fetuses improved dynamic lung compliance by about 30% compared with untreated controls.Keywords : pulmonary surfactant; surfactant protein B ; surfactant protein C ; transmembrane peptide; amphipathic peptide.

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“…These associated vesicles are difficult to wash away with extensive flushing of the subphase, even in the absence of calcium ions, indicating that these are firmly attached to the monolayer. There are evidences that SP-B and mostly the palmitoyl chain of SP-C facilitate formation of surface associated surfactant-reservoir by bridging the monolayer to the lipid bilayers underneath [Qanbar et al, 1996]. Model studies suggest that there exists a continuous and dynamic flow of surface active lipid species between the monolayer directly located at the interface and the associated bilayer structures [Perez-Gil, 2002].…”

Section: Formation Of Surfactant Reservoirmentioning

confidence: 99%

“…This correlates well with secondary structure analysis by circular dichroism and FT-IR [Pastrana et al, 1991]. In contrast to SP-B, there are only a few activities of SP-C, which mostly overlap with SP-B's activities, e.g., promotion of lipid adsorption onto the air-liquid interface, re-spreading of films from their collapse phase, re-uptake of surfactant by type II cells, and stabilization of the monolayer lipid film [Qanbar et al, 1996]. All these functions are extracellular, and except for surfactant re-uptake, it also contributes to film homeostasis.…”

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confidence: 99%

Physiologically Essential Pulmonary Surfactants: A Brief Physicochemical Account

Panda

2017

Proceedings of the Indian National Science Academy

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Pulmonary surfactant (PS) is a complex mixture of lipids and proteins that forms a monomolecular film at the lung-air interface. It serves dual purposes: (i) lowers the surface tension; and (ii) participates in innate immune defense of the lung. Surface tension lowering property of PS is achieved by forming a surface film (monolayer) which is highly enriched in dipalmitoylphosphatidylcholine. Among the four surfactant proteins (SP), SP-A and SP-D are hydrophilic, SP-B and SP-C are hydrophobic and are also biocompatible in all the mammalians. This article gives a brief account of the history of research on PS, anatomy of lung, alveolar metabolism, composition and methodologies adopted for in vitro evaluation of the PS.The possible molecular mechanism of film formation (adsorption), and of film adaptation to surface changes (phase transitions) during the process of respiration have been described in detail. Major disorders of the surfactant system related with its clinical consequence, and the potentials of surfactant therapy in the treatment of some of these disorders have been discussed.A brief account of the evolutionary development of pulmonary surfactants has also been presented. Keywords BackgroundIn the 1950s and 1960s, a respiratory disease, misleadingly named hyaline membrane disease (HMD), was the world's most common cause of infant morbidity, especially among the preterm babies. The infant morbidity led to the need of search for the understanding of lung function.Scientists and clinicians, working together, discovered the existence and necessity of pulmonary surfactant (PS) and then attempted to figure out how to overcome its dysfunction. The year 1929 is considered as the starting date in the history of PS when Kurt von Neergaard's experiments revealed that the required pressure for filling the lungs with air was higher than filling it with liquid [Von Neergard, 1929]. The alveoli can achieves near zero surface tension at the lung-air interface following the principle of the Young and Laplace. In 1946, it was reported that lung tissue has a remarkably high content of the lipid, dipalmitoyllecithin (currently known as dipalmitoylphosphatidylcholine). Studies on the effects of nerve gases on lungs, significantly contributed to the understanding of the physiology of PS [Clements, 1957]. It was proposed that alveoli, made of lung fluid material, can achieve substantial stability through the quantity and quality of the surface-active materials available at the lung-air interface. Subsequently, with the help of modified surface balance, it could be demonstrated that surface tension can drop to low values upon compression of surface films from lung extracts [Klaus et al., 1961]. There exists similarity in surface activity of dipalmitoylphosphatidylcholine (DPPC) and the phospholipids isolated from freshly lavaged bovine lung. HMD, now known as respiratory distress syndrome (RDS), is due to the deficiency or dysfunction of PS [Avery and Mead, 1959]. Since 1959, scientists from various disciplines flocked to...

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Role of the palmitoylation of surfactant-associated protein C in surfactant film formation and stability

Cited by 42 publications

References 0 publications

Lipid compositional analysis of pulmonary surfactant monolayers and monolayer-associated reservoirs

Lipid compositional analysis of pulmonary surfactant monolayers and monolayer-associated reservoirs

Synthetic peptide‐containing surfactants

Physiologically Essential Pulmonary Surfactants: A Brief Physicochemical Account

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