Effect of reconstituted pulmonary surfactant containing the 6000-dalton hydrophobic protein on lung compliance of prematurely delivered rabbit fetuses.
Chloroform:methanol extracts of bovine pulmonary surfactant contain small hydrophobic proteins, designated surfactant-associated apoproteins 6,000 (SAP-6), but do not contain the major surfactant-associated 35,000-dalton glycoprotein, designated SAP-35. Examination of lipid extract surfactant on sodium dodecylsulfate-polyacrylamide gel electrophoresis revealed hydrophobic proteins with apparent molecular masses of 15,000, 7,000, and 3,5000 daltons prior to reduction. After reduction, the 15,000-dalton species largely disappeared and was replaced by a 5,000-dalton species. In addition, the 7000- and 3500-dalton species exhibited a slightly enhanced mobility. Amino acid analysis demonstrated that SAP-6 possesses a more highly hydrophobic profile than SAP-35. Combining the protein-containing fractions from silicic acid chromatography of lipid extract with synthetic dipalmitoylphosphatidylcholine produced a reconstituted surfactant preparation which was just as active as lipid extract surfactant on a pulsating bubble surfactometer. The reconstituted surfactant contained SAP-6 but not SAP-35. Pressure-volume studies revealed that, at the optimal dose, reconstituted surfactant containing half the SAP-6 concentration of lipid extract exhibited similar effectiveness to lipid extract surfactant in promoting lung expansion with prematurely delivered rabbit fetuses of 27 days gestation. Reconstituted surfactant with an identical SAP-6 protein concentration as lipid extract possessed the same biological properties as the preparation with 1% SAP-6 protein. These studies support the view that an artificial surfactant composed of synthetic or semisynthetic lipids plus human SAP-6 produced via biotechnology could be useful for prevention and/or treatment of the neonatal respiratory distress syndrome.
Yu
S H
SH
Department of Obstetrics and Gynaecology, University of Western Ontario, London, Canada.
Wallace
D
D
Bhavnani
B
B
Enhorning
G
G
Harding
P G
PG
Possmayer
F
F
D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D005333:Fetus / Q000187:drug effects; D008168:Lung / Q000196:embryology; D008170:Lung Compliance / Q000187:drug effects*; D008970:Molecular Weight; D011510:Proteolipids / Q000032:analysis / Q000494:pharmacology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000031:analogs & derivatives*; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000032:analysis / Q000494:pharmacology*; D011817:Rabbits
D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C445842:SFTPA1 protein, human