Hydrophobic Surfactant-Associated Protein in Whole Lung Surfactant and Its Importance for Biophysical Activity in Lung Surfactant Extracts Used for Replacement Therapy

Whitsett, Jeffrey A.; Ohning, Bryan L.; Ross, Gary F.; Meuth, Joseph L.; Weaver, Timothy E.; Holm, B. A.; Shapiro, Donald L.; Notter, Robert H.

doi:10.1203/00006450-198605000-00016

Cited by 216 publications

(106 citation statements)

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“…These features suggest a structural role for SP-C in facilitating the movement of phospholipids between multilayered films. Biological functions of purified SP-C or synthetic SP-C peptides are highly active in vitro and in vivo, enhancing surfactant properties of lipids and restoring lung function in surfactant-deficient animals (6,7). These results indicate that SP-C plays an important role in the spreading and stabilization of phospholipid films in the alveolus.…”

mentioning

confidence: 68%

Pneumonitis and Emphysema in sp-C Gene Targeted Mice

Glasser¹,

Detmer²,

Ikegami³

et al. 2003

Journal of Biological Chemistry

202

161

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confidence: 68%

Pneumonitis and Emphysema in sp-C Gene Targeted Mice

Glasser¹,

Detmer²,

Ikegami³

et al. 2003

Journal of Biological Chemistry

202

161

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“…The importance of these apoproteins, termed SP-B and SP-C (20) in the ability of natural or synthetic surfactants to be able to reduce surface tension at the epithelial air/liquid interface in the lung has been the subject of several recent papers (2,7,10,11,(13)(14)(15)(17)(18)(19)(21)(22)(23). Human surfactant isolated from term amniotic fluid (24)(25)(26), as well as heterologous surfactants consisting of lung mince or airway lavage lipid extracts from calves Sephadex LH-60 (Pharmacia Fine Chemicals, Uppsala, Sweden) column.…”

Section: Preparation Ofpurified Sp-b Monomer Dimer and Oligomersmentioning

confidence: 99%

“…The presence of two hydrophobic, low molecular weight apoproteins in mammalian pulmonary surfactant has been shown (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), and cDNA clones have been isolated that predict the amino acid sequences of their precursor molecules (3-5, 10, 15). The importance of these apoproteins, termed SP-B and SP-C (20) in the ability of natural or synthetic surfactants to be able to reduce surface tension at the epithelial air/liquid interface in the lung has been the subject of several recent papers (2,7,10,11,(13)(14)(15)(17)(18)(19)(21)(22)(23).…”

Section: Preparation Ofpurified Sp-b Monomer Dimer and Oligomersmentioning

confidence: 99%

“…Figure 2 shows the molecular weight characteristics of the various SP-B forms separated on this column. Pools were made of oligomer/dimer (fractions II and 12), dimer (fractions 13 and 14), and monomer (fractions [16][17][18][19]. The pools were dried under N 2 , lyophilized for I h, redissolved in 500~L methanol, and quantitated by amino acid compositional analysis.…”

Section: Preparation Ofpurified Sp-b Monomer Dimer and Oligomersmentioning

confidence: 99%

“…SP-B, also called SP-18 (4,10), SPL(Phe) (3), PSP-B (5), and SAP-6-14 (7,16,17,23), has been shown to be a disulfide-linked dimer of two identical polypeptides of approximately 9000 D having an amino terminal sequence of phe-pro-ile-pro-leu-pro-tyr-(human) (3,5,10). Data based on amino acid compositions (10) and fast atom bombardment mass spectroscopy (unpublished observations) have led us to conclude that human SP-B is 80-81 residues in length.…”

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The Use of Synthetic Peptides in the Formation of Biophysically and Biologically Active Pulmonary Surfactants

et al. 1991

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ABSTRACf. Synthetic pulmonary surfactants consisting of mixtures of phospholipids with synthetic peptides based on the amino acid sequence of human surfactant apoprotein SP-B were prepared. These surfactants were analyzed for their ability to lower surface tension on a pulsating bubble surfactometer and for their capacity to improve lung compliance and increase alveolar expansion in a fetal rabbit model of surfactant deficiency. The data demonstrate that several peptides, ranging from 17 to 45 residues in length, matching the carboxy-terminal sequence of the SP-B protein, when appropriately recombined with the phospholipids dipalmitoylphosphatidylcholine and phosphatidylglycerol (3:1), are capable of producing a synthetic surfactant with biophysical and biologicactivity approaching that of human surfactant derived from amniotic fluid. (Pediatr Res 29: 460-465, 1991) Abbreviations DPPC, dipalmitoylphosphatidylcholine lA, iodoacetic acid PG, phosphatidylglycerol PL, phospholipid SP, surfactant protein or swine, or synthetic lipids, generally in combination with SPBand SP-C (7, 10, 11, 13-15, 17-19, 21-23, 27), are being evaluated for their potential use in surfactant replacement therapies.Our previous studies (10) and those of Curstedt et al. (2), and Yu and Possmayer (19), suggested that when recombined with PL, SP-B resulted in greater surface tension lowering and biologic activity than did SP-C. For this reason, we decided to focus our attention on this protein. SP-B, also called SP-18 (4, 10), SPL(Phe) (3), PSP-B (5), and SAP-6-14 (7,16,17,23), has been shown to be a disulfide-linked dimer of two identical polypeptides of approximately 9000 D having an amino terminal sequence of phe-pro-ile-pro-leu-pro-tyr-(human) (3, 5, 10). Data based on amino acid compositions (10) and fast atom bombardment mass spectroscopy (unpublished observations) have led us to conclude that human SP-B is 80-81 residues in length. The sequence is shown in Figure I.To investigate the mechanisms by which SP-B protein augments the surfactant capacity of PL, peptides were synthesized that conform to portions of the native sequence of this protein. These peptides could be combined with PL to reconstitute the biophysical and biologic activities of natural surfactant. We report here the results of studies, using the pulsating bubble surfactometer to measure the capacity of these synthetic surfactants to lower surface tension at an air/liquid interface and the fetal rabbit model to determine their ability to increase lung compliance and alveolar expansion. MATERIALS AND METHODS Preparation ofpurified SP-B monomer, dimer, and oligomers.SP-B was isolated from human amniotic fluid surfactant ad escribed previously (10). One hundred J.Lg of SP-B, in a volume of 206 J.LL methanol, were incubated with 5.14 mg DTT (Sigma Chemical Co, St. Louis, MO) in 17 J.LL methanol, for 1 h at 37°C. Analysis of 2 J.LL on SDS-PAGE showed the SP-B to be approximately 70% reduced as noted by a shift in band position from 18000 D to approximately 9000 D. The SP-B/...

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Effect of Exogenous Surfactant (Calfactant) in Pediatric Acute Lung Injury<SUBTITLE>A Randomized Controlled Trial</SUBTITLE>

Willson

Thomas

Markovitz

et al. 2005

JAMA

374

279

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CUTE RESPIRATORY DISTRESS syndrome (ARDS) was originally termed the adult respiratory distress syndrome because it resembled the clinical picture of infant respiratory distress syndrome (IRDS), and both exhibited hyaline membranes at autopsy. 1,2 Avery and Mead 3 first reported that lung surfactant quantity and activity were abnormal in infants with IRDS and surfactant replacement has subsequently become standard therapy for premature infants at risk for or having IRDS. Petty and Ashbaugh 2 described qualitative and quantitative surfactant deficiencies in their initial description of ARDS and the subsequent scientific literature (recently reviewed by Notter 4) has supported the role of surfactant dysfunction in both ARDS and less severe acute lung injury (ALI). 5 Surfactant replacement in ARDS and ALI has been Author Affiliations and Participating Hospitals and Collaborating Investigators are listed at the end of this article. Financial Disclosures: Dr Willson has received research grants from ONY Inc (Amherst, NY). Dr Egan is president and equity owner of ONY Inc.

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Hydrophobic Surfactant-Associated Protein in Whole Lung Surfactant and Its Importance for Biophysical Activity in Lung Surfactant Extracts Used for Replacement Therapy

Cited by 216 publications

References 50 publications

Pneumonitis and Emphysema in sp-C Gene Targeted Mice

Pneumonitis and Emphysema in sp-C Gene Targeted Mice

The Use of Synthetic Peptides in the Formation of Biophysically and Biologically Active Pulmonary Surfactants

Effect of Exogenous Surfactant (Calfactant) in Pediatric Acute Lung Injury<SUBTITLE>A Randomized Controlled Trial</SUBTITLE>

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