Abstract
Background:
Pulmonary surfactant provides an alveolar surface-active film that is critical for normal lung function. Our objective was to determine in vitro film formation properties of therapeutic and infant surfactants and the influence of surfactant protein (SP)-B content.
Methods:
We used a multiwell fluorescent assay measuring maximum phospholipid surface accumulation (Max), phospholipid concentration required for half-maximal film formation (½Max), and time for maximal accumulation (tMax).
Results:
Among five therapeutic surfactants, calfactant (highest SP-B content) had film formation values similar to natural surfactant, and addition of SP-B to beractant (lowest SP-B) normalized its Max value. Addition of budesonide to calfactant did not adversely affect film formation. In tracheal aspirates of preterm infants with evolving chronic lung disease, SP-B content correlated with ½Max and tMax values, and SP-B supplementation of SP-B-deficient infant surfactant restored normal film formation. Reconstitution of normal surfactant indicated a role for both SP-B and SP-C in film formation.
Conclusion:
Film formation in vitro differs among therapeutic surfactants and is highly dependent on SP-B content in infant surfactant. The results support a critical role of SP-B for promoting surface film formation.
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References
Merrill JD, Ballard RA, Cnaan A, et al. Dysfunction of pulmonary surfactant in chronically ventilated premature infants. Pediatr Res 2004;56:918–26.
Hawgood S . Surfactant protein B: structure and function. Biol Neonate 2004;85:285–9.
Taeusch HW, Bernardino de la Serna J, Perez-Gil J, Alonso C, Zasadzinski JA . Inactivation of pulmonary surfactant due to serum-inhibited adsorption and reversal by hydrophilic polymers: experimental. Biophys J 2005;89:1769–79.
Polin RA, Carlo WA ; Committee on Fetus and Newborn; American Academy of Pediatrics. Surfactant replacement therapy for preterm and term neonates with respiratory distress. Pediatrics 2014;133:156–63.
Sinha SK, Lacaze-Masmonteil T, Valls i Soler A, et al.; Surfaxin Therapy Against Respiratory Distress Syndrome Collaborative Group. A multicenter, randomized, controlled trial of lucinactant versus poractant alfa among very premature infants at high risk for respiratory distress syndrome. Pediatrics 2005;115:1030–8.
Sato A, Ikegami M . SP-B and SP-C containing new synthetic surfactant for treatment of extremely immature lamb lung. PLoS One 2012;7:e39392.
Seehase M, Collins JJ, Kuypers E, et al. New surfactant with SP-B and C analogs gives survival benefit after inactivation in preterm lambs. PLoS One 2012;7:e47631.
Yeh TF, Lin HC, Chang CH, et al. Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: a pilot study. Pediatrics 2008;121:e1310–8.
Enhorning G . Pulmonary surfactant function studied with the pulsating bubble surfactometer (PBS) and the capillary surfactometer (CS). Comp Biochem Physiol A Mol Integr Physiol 2001;129:221–6.
Ravasio A, Cruz A, Pérez-Gil J, Haller T . High-throughput evaluation of pulmonary surfactant adsorption and surface film formation. J Lipid Res 2008;49:2479–88.
Notter RH, Wang Z, Egan EA, Holm BA . Component-specific surface and physiological activity in bovine-derived lung surfactants. Chem Phys Lipids 2002;114:21–34.
Blanco O, Pérez-Gil J . Biochemical and pharmacological differences between preparations of exogenous natural surfactant used to treat Respiratory Distress Syndrome: role of the different components in an efficient pulmonary surfactant. Eur J Pharmacol 2007;568:1–15.
Ballard PL, Merrill JD, Godinez RI, Godinez MH, Truog WE, Ballard RA . Surfactant protein profile of pulmonary surfactant in premature infants. Am J Respir Crit Care Med 2003;168:1123–8.
Merrill JD, Ballard PL, Courtney SE, et al. Pilot trial of late booster doses of surfactant for ventilated premature infants. J Perinatol 2011;31:599–606.
Zuo YY, Veldhuizen RA, Neumann AW, Petersen NO, Possmayer F . Current perspectives in pulmonary surfactant–inhibition, enhancement and evaluation. Biochim Biophys Acta 2008;1778:1947–77.
Serrano AG, Pérez-Gil J . Protein-lipid interactions and surface activity in the pulmonary surfactant system. Chem Phys Lipids 2006;141:105–18.
Takamoto DY, Lipp MM, von Nahmen A, Lee KY, Waring AJ, Zasadzinski JA . Interaction of lung surfactant proteins with anionic phospholipids. Biophys J 2001;81:153–69.
Lopez-Rodriguez E, Echaide M, Cruz A, Taeusch HW, Perez-Gil J . Meconium impairs pulmonary surfactant by a combined action of cholesterol and bile acids. Biophys J 2011;100:646–55.
Krüger P, Schalke M, Wang Z, Notter RH, Dluhy RA, Lösche M . Effect of hydrophobic surfactant peptides SP-B and SP-C on binary phospholipid monolayers. I. Fluorescence and dark-field microscopy. Biophys J 1999;77:903–14.
Mizuno K, Ikegami M, Chen CM, Ueda T, Jobe AH . Surfactant protein-B supplementation improves in vivo function of a modified natural surfactant. Pediatr Res 1995;37:271–6.
Durand DJ, Clyman RI, Heymann MA, et al. Effects of a protein-free, synthetic surfactant on survival and pulmonary function in preterm lambs. J Pediatr 1985;107:775–80.
Guardia CG, Moya FR, Sinha S, Simmons PD, Segal R, Greenspan JS . A pharmacoeconomic analysis of in-hospital costs resulting from reintubation in preterm infants treated with lucinactant, beractant, or poractant alfa. J Pediatr Pharmacol Ther 2012;17:220–7.
Yu SH, McCormack FX, Voelker DR, Possmayer F . Interactions of pulmonary surfactant protein SP-A with monolayers of dipalmitoylphosphatidylcholine and cholesterol: roles of SP-A domains. J Lipid Res 1999;40:920–9.
Palmer D, Schürch S, Belik J . Effect of budesonide and salbutamol on surfactant properties. J Appl Physiol (1985) 2000;89:884–90.
King RJ, Clements JA . Surface active materials from dog lung. 3. Thermal analysis. Am J Physiol 1972;223:727–33.
Keller RL, Merrill JD, Black DM, et al. Late administration of surfactant replacement therapy increases surfactant protein-B content: a randomized pilot study. Pediatr Res 2012;72:613–9.
Cogo PE, Simonato M, Danhaive O, et al. Impaired surfactant protein B synthesis in infants with congenital diaphragmatic hernia. Eur Respir J 2013;41:677–82.
Subramaniam S, Bummer P, Gairola CG . Biochemical and biophysical characterization of pulmonary surfactant in rats exposed chronically to cigarette smoke. Fundam Appl Toxicol 1995;27:63–9.
Bartlett GR . Phosphorus assay in column chromatography. J Biol Chem 1959;234:466–8.
Cogo P, Baritussio A, Rosso F, et al. Surfactant-associated protein B kinetics in vivo in newborn infants by stable isotopes. Pediatr Res 2005;57:519–22.
Acknowledgements
We are grateful to H.W. Taeusch for reviewing the manuscript; J.A. Clements for providing colfosceryl palmitate; Ony Inc., Amherst, VA, and Discovery Laboratories, Warrington, PA, for providing calfactant and lucinactant, respectively.
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Danhaive, O., Chapin, C., Horneman, H. et al. Surface film formation in vitro by infant and therapeutic surfactants: role of surfactant protein B. Pediatr Res 77, 340–346 (2015). https://doi.org/10.1038/pr.2014.176
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DOI: https://doi.org/10.1038/pr.2014.176
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