Anionic Polymers Reverse Serum Inhibition of Pulmonary Surfactant by Promoting Accumulation of Surfactant Near the Air-Liquid Interface

Abstract

Acute respiratory distress syndrome (ARDS) is a common pathology, including a spectrum of respiratory diseases associated with lung injury, and exhibiting a high overall mortality and morbidity rate. Inactivation of surfactant by serum and inflammatory components leaked into the alveolar spaces is considered as an important pathogenic factor within ARDS.The mechanism by which inhibition is taking place depends on the nature of the inhibitory substance and could affect either the ability of surfactant to adsorb into the air-water interface or the ability of surfactant films themselves to reach the lowest surface tensions along the compression-expansion breathing cycles. Up to now, different polymers have proven to be useful to reverse or prevent inactivation of surfactant. We have explored the performance of inhibited surfactant and potential reactivating conditions using a fluorescent high-throughput method that detects and quantitates accumulation of surfactant near the air-liquid interface. This accumulation can be correlated in a first step with the concomitant decrease in surface tension that occurs when surface active lipids are transferred into the air-exposed side. Using this method we have evaluated inhibition of native porcine surfactant and of several clinical surfactants by serum, and the ability of hyaluronic acid (HA) to reverse or prevent this inhibition. A comparison was also made with the effect of other polymers. In general terms, presence of polymers in the subphase increases significantly the amount of surfactant associated with interfacial regions and seems to overcome, at least partially, the barrier to adsorption imposed by serum. Results obtained from a massive number of samples showed a very high reproducibility and a high correlation with data obtained using traditional methods to assess surfactant activity, such as surface balances or the Captive Bubble Surfactometer.