Abstract
Surfactant replacement is an effective therapy for neonatal respiratory distress syndrome. Full recovery from respiratory distress syndrome requires development of endogenous surfactant synthesis and metabolism. The influence of exogenous surfactant on the development of surfactant synthesis in premature lungs is not known. We hypothesized that different exogenous surfactants have different effects on the development of endogenous surfactant production in the premature lung. We treated organ cultures of d 25 fetal rabbit lung for 3 d with 100 mg/kg body weight of natural rabbit surfactant, Survanta, and Exosurf and measured their effects on the development of surfactant synthesis. Additional experiments tested how these surfactants and Curosurf affected surfactant protein (SP) SP-A, SP-B, and SP-C mRNA expression. Surfactant synthesis was measured as the incorporation of 3H-choline and 14C-glycerol into disaturated phosphatidylcholine recovered from lamellar bodies. Randomized-block ANOVA showed significant differences among treatments for incorporation of both labels (p < 0.01), with natural rabbit surfactant less than control, Survanta greater than control, and Exosurf unchanged. Additional experiments with natural rabbit surfactant alone showed no significant effects in doses up to 1000 mg/kg. Survanta stimulated disaturated phosphatidylcholine synthesis (173 ± 41% of control;p = 0.01), increased total lamellar body disaturated phosphatidylcholine by 22% (p < 0.05), and increased 14C-disat-PC specific activity by 35% (p < 0.05). The response to Survanta was dose-dependent up to 1000 mg/kg. Survanta did not affect surfactant release. No surfactant altered the expression of mRNA for SP-A, SP-B, or SP-C. We conclude that surfactant replacement therapy can enhance the maturation of surfactant synthesis, but this potential benefit differs with different surfactant preparations.
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Abbreviations
- DPPC:
-
dipalmitoyl phosphatidylcholine
- disat-PC:
-
disaturated phosphatidylcholine
- LB:
-
lamellar body
- NARS:
-
natural adult rabbit surfactant
- PC:
-
phosphatidylcholine
- PG:
-
phosphatidylglycerol
- PI:
-
phosphatidylinositol
- RDS:
-
neonatal respiratory distress syndrome
- SP-A:
-
surfactant protein A
- SP-B:
-
surfactant protein B
- SP-C:
-
surfactant protein C
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Acknowledgements
The authors thank Professor P. Burri for support and reviewing of the manuscript, and Drs. F. Possmeyer and M. Shen for their helpful advice and contributions.
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Supported by NIH grant HL37930, a grant from Chiesi Pharmaceuticals, and reagents from Dey Laboratories and Ross Laboratories.
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Amato, M., Petit, K., Fiore, H. et al. Effect of Exogenous Surfactant on the Development of Surfactant Synthesis in Premature Rabbit Lung. Pediatr Res 53, 671–678 (2003). https://doi.org/10.1203/01.PDR.0000054655.95452.06
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DOI: https://doi.org/10.1203/01.PDR.0000054655.95452.06
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