Inactivation of pulmonary surfactant and its prevention

Pulmonary surfactant is a lipoprotein complex coating the conducting airways down to the terminal airspaces. Its main function is to lower surface tension at the air liquid interface thus preventing alveolar collapse at end expiration. Primary surfactant deficiency is the main cause of neonatal respiratory distress syndrome (RDS) and treatment with exogenous pulmonary surfactant improves the course of the disease significantly. Furthermore, secondary surfactant deficiency caused by inactivation of endogenous surfactant occurs in older patients with acute RDS (ARDS), pneumonia or meconium aspiration syndrome (MAS).

Abnormal alveolar presence of substances like aspirated meconium or leaking serum proteins inhibits surface activity. This inactivation of endogenous surfactant can be overcome by increasing the surfactant concentration with exogenous surfactant. In the clinical setting modified natural surfactants extracted from animal lungs are used most commonly. However, a new generation of surfactant preparations containing synthetic proteins are currently under development to improve supply and to lower costs.

In our project we investigated the sensitivity of exogenous surfactant preparations to different types of inactivation and tried to find ways for improving their resistance. In vitro we found new synthetic surfactant containing proteins to be more resistant to meconium inactivation than modified natural surfactants. Meconium induced inactivation of modified natural surfactant was reversible, especially in the presence of calcium or polymyxin B (PxB), a cross linking protein of phospholipid films with antimicrobial properties. PxB enriched surfactant also preserves antibiotic characteristics in vitro and in an animal model of neonatal pneumonia.

Accidentally, we observed surfactant inactivation by silicone oil dissolved from syringes that are in clinical use. This type of inactivation may lead to significant deterioration of lungs in an animal model of RDS. By comparison of surfactant preparations comprising the hydrophobic surfactant protein B and/or C we pointed out that both proteins are needed for alveolar stability.

List of scientific papers

I. Herting E, Rauprich P, Stichtenoth G, Walter G, Johansson J, Robertson B (2001). Resistance of different surfactant preparations to inactivation by meconium. Pediatr Res. 50(1): 44-9
https://pubmed.ncbi.nlm.nih.gov/11420417

II. Herting E, Stichtenoth G, Robertson B (2003). Syringes with rubber-coated plungers and inactivation of surfactant. Lancet. 361(9354): 311-3
https://pubmed.ncbi.nlm.nih.gov/12559869

III. Stichtenoth G, Jung P, Walter G, Johansson J, Robertson B, Curstedt T, Herting E (2006). Polymyxin B/pulmonary surfactant mixtures have increased resistance to inactivation by meconium and reduce growth of gram-negative bacteria in vitro. Pediatr Res. 59(3): 407-11
https://pubmed.ncbi.nlm.nih.gov/16492980

IV. Almlén A, Stichtenoth G, Linderholm B, Haegerstrand-Björkman M, Robertson B, Johansson J, Curstedt T (2008). Surfactant proteins B and C are both necessary for alveolar stability at end expiration in premature rabbits with respiratory distress syndrome. J Appl Physiol. 104(4): 1101-8. Epub 2008 Feb 14
https://pubmed.ncbi.nlm.nih.gov/18276900

V. Stichtenoth G, Linderholm B, Almlén A, Björkman MH, Byman I, Nordling K, Robertson B, Johansson J, Herting E, Curstedt T (2009). Inactivation of pulmonary surfactant by silicone oil in vitro and in ventilated immature rabbits. Crit Care Med. 37(5): 1750-6
https://pubmed.ncbi.nlm.nih.gov/19325472

VI. Stichtenoth G, Linderholm B, Hägerstrand Björkman M, Walter G, Curstedt T, Herting E (2009). Prophylactic intratracheal administration of polymyxin B /surfactant mixtures prevents bacterial growth and maintains compliance in E.coli pneumonia of newborn rabbits. [Submitted]