Abstract
Surfactant protein A (SP-A) is a 248-residue, water-soluble, lipid-associating protein found in lung surfactant. Analysis of the amino acid sequence using the Eisenberg hydrophobic moment algorithm predicts that the SP-A segment spanning residues 114-144 has high hydrophobic moments, typical of lipid-associating amphipathic domains. The secondary structure, in vitro surface activity and in vivo lung activity of this SP-A sequence were studied with a 31-residue synthetic peptide analog(A114-144). Analysis of the secondary structure using circular dichroism and Fourier transform infrared spectroscopy indicated association with lipid dispersions and a dominant helical content. Surface activity measurements of A114-144 with surfactant lipid dispersions and the hydrophobic surfactant proteins B and C (SP-B/C) showed that A114-144 enhances surface activity under conditions of dynamic compression and respreading on a Langmuir/Wilhelmy surface balance. Synthetic surfactant dispersions containing A114-144 improved lung compliance in spontaneously breathing, 28-d premature rabbits to a greater degree than surfactant dispersions with synthetic SP-B/C and synthetic surfactant lipids alone. These observations indicate that inclusion of A114-144 may improve synthetic preparations currently used for surfactant replacement therapy.
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Abbreviations
- SP-A, -B, -C, -D:
-
surfactant proteins A, B, C, D
- A114-144:
-
SP-A residues 114-144
- B/C:
-
synthetic SP-B and SP-C
- CD:
-
circular dichroism
- DPPC:
-
dipalmitoylphosphatidylcholine
- FTIR:
-
Fourier transform infrared spectroscopy
- PL:
-
phospholipid
- TFE:
-
trifluoroethanol
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Acknowledgements
The authors thank Dr. Larry Vicekery, University of California, Irvine, and Dr. Vern Shoemaker, UCLA, for the use of the Jasco J-720 and J-600 CD spectrometers. Survanta was donated by Ross Laboratories (Columbus, OH).
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Supported by National Institutes of Health Grants HL 55534, GM 50483, and RCMI G12 RR 3026, and by March of Dimes Grant 93-0739. R.B. is a Parker B. Francis Fellow in Pulmonary Research.
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Walther, F., David-Cu, R., Leung, C. et al. A Synthetic Segment of Surfactant Protein A: Structure, in Vitro Surface Activity, and in Vivo Efficacy. Pediatr Res 39, 938–946 (1996). https://doi.org/10.1203/00006450-199606000-00003
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DOI: https://doi.org/10.1203/00006450-199606000-00003
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