Surface properties of sulfur- and ether-linked phosphonolipids with and without purified hydrophobic lung surfactant proteins

Chang, Yusuo; Wang, Zhengdong; Schwan, Adrian L.; Wang, Zhongyi; Holm, Bruce A.; Baatz, John E.; Notter, Robert H.

doi:10.1016/j.chemphyslip.2005.07.002

Cited by 19 publications

(42 citation statements)

References 40 publications

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“…Ester-linked glycerophospholipids of the kind found in native surfactant are the primary lipids used in current synthetic exogenous surfactants. However, synthetic ether-linked lipids are now available that have direct structural analogy to lung surfactant lipids plus designed molecular behavior that enhances adsorption and spreading while maintaining very high dynamic surface tension lowering in surface films (e.g., [71,[205][206][207][208][209][210][211]). Moreover, such lipids have structural features making them resistant to phospholipases such as phospholipase A 2 , which has been implicated in the pathology of ALI/ARDS [65,[212][213][214][215][216][217][218].…”

Section: Examples Of Research On New Synthetic Exogenous Surfactamentioning

confidence: 99%

“…Phospholipase-induced degradation of lung surfactant glycerophospholipids not only reduces the concentration of active components, but also generates reaction products such as lysophosphatidylcholine and fluid free fatty acids that can further decrease surface activity by interacting biophysically with remaining surfactant at the alveolar interface [55,59,70]. Synthetic exogenous surfactants containing such phosphonolipids combined with purified surfactant proteins or synthetic peptides have very high overall surface activity plus an ability to resist phospholipases in ALI/ARDS [71,[208][209][210][211]219]. On-going basic research is continuing to design and synthesize peptides related to SP-B and other surfactant proteins for use in highly-active fully-synthetic exogenous surfactants in combination with either normal glycerophospholipids or phospholipase-resistant analogs.…”

Section: Examples Of Research On New Synthetic Exogenous Surfactamentioning

confidence: 99%

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Surfactant for Pediatric Acute Lung Injury

Willson¹,

Chess²,

Notter³

2008

Pediatric Clinics of North America

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SynopsisThis article reviews exogenous surfactant therapy and its use in mitigating acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in infants, children, and adults. Biophysical and animal research documenting surfactant dysfunction in ALI/ARDS is described, and the scientific rationale for treatment with exogenous surfactant is discussed. Major emphasis is on reviewing clinical studies of surfactant therapy in pediatric and adult patients with ALI/ARDS. Particular advantages from surfactant therapy in direct pulmonary forms of these syndromes are described. Also discussed are additional factors affecting the efficacy of exogenous surfactants in ALI/ARDS, including the multifaceted pathology of inflammatory lung injury, the effectiveness of surfactant delivery in injured lungs, and composition-based activity differences among clinical exogenous surfactant preparations.

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Section: Examples Of Research On New Synthetic Exogenous Surfactamentioning

confidence: 99%

Section: Examples Of Research On New Synthetic Exogenous Surfactamentioning

confidence: 99%

Surfactant for Pediatric Acute Lung Injury

Willson¹,

Chess²,

Notter³

2008

Pediatric Clinics of North America

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“…DEPN-8 [(6)-trimethyl(3-phosphonopropyl)ammonium, mono(2,3-bis(hexadecyloxy)propyl) ester] was synthesized and purified using our previously published methods (14,15,20). The chemical scheme for preparing DEPN-8 used the conversion of (6)-1-hexadecyloxy-2,3-propanediol to (6)-2,3-bis(hexadecyloxy)-1-propanol by way of hydroxyl protection at the 3-position, alkylation at the 2-hydroxyl group, and deprotection.…”

Section: Surfactant Substancesmentioning

confidence: 99%

“…At a mechanistic level, a major factor in the resistance of DEPN-8 1 1.5% SP-B/C to activity inhibition from PLA 2 is the molecular structural resistance of DEPN-8 to chemical degradation by this enzyme (14,20). Phospholipases can be present in the pulmonary interstitium and alveoli during inflammatory lung injury (3-10), and PLA 2 has been proposed as having specific importance in the pathogenesis of ARDS (5,40).…”

Section: Table 2 Calculated Percent Volume Recoveries At Low Transpumentioning

confidence: 99%

“…DEPN-8 also can form interdigitated bilayers, which may contribute to its improved respreading and adsorption relative to DPPC (19). Recent studies by Wang and coworkers (14) and Chang and colleagues (20) have shown that a model exogenous surfactant containing DEPN-8 1 1.5% bovine surfactant protein (SP)-B/C has very high surface activity and resistance to inhibition by phospholipase A 2 (PLA 2 ) in vitro. This work is extended here to define the physiologic activity and inhibition resistance of this surfactant in the excised, lavaged rat lung model of Bermel and coworkers (21).…”

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Activity and Inhibition Resistance of a Phospholipase-Resistant Synthetic Surfactant in Rat Lungs

Wang¹,

Chang²,

Schwan³

et al. 2007

Am J Respir Cell Mol Biol

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This study investigates the activity and inhibition resistance in excised rat lungs of a novel synthetic surfactant containing the phospholipase-resistant diether phosphonolipid DEPN-8 plus 1.5% bovine surfactant protein (SP)-B/C compared to calf lung surfactant extract (CLSE). DEPN-8 1 1.5% SP-B/C surpassed CLSE in normalizing surfactant-deficient pressure-volume (P-V) deflation mechanics in lavaged excised lungs in the presence of phospholipase A 2 (PLA 2 ) or C18:1 lyso-phosphatidylcholine (LPC). DEPN-8 1 1.5% SP-B/C had activity equal to CLSE in normalizing P-V mechanics in the absence of inhibitors or in the presence of serum albumin. These physiologic activity findings were directly consistent with surface activity measurements on the pulsating bubble surfactometer. In the absence of inhibitors, DEPN-8 1 1.5% SP-B/C and CLSE rapidly reached minimum surface tensions , 1 mN/m (0.5 and 2.5 mg surfactant phospholipid/ ml). DEPN-8 1 1.5% SP-B/C maintained its high surface activity in the presence of PLA 2 , while the surface activity of CLSE was significantly inhibited by exposure to this enzyme. DEPN-8 1 1.5% SP-B/C also had greater surface activity than CLSE in the presence of LPC, and the two surfactants had equivalent surface activity in the presence of albumin. DEPN-8 1 1.5% SP-B/C also had slightly greater surface activity than CLSE when exposed to peroxynitrite in pulsating bubble studies. These results support the potential of developing highly active and inhibition-resistant synthetic exogenous surfactants containing DEPN-8 1 apoprotein/peptide constituents for use in treating direct pulmonary forms of clinical acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS).

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