The Role of Cholesterol in Lung Surfactant

Lung surfactant, a complex mixture of lipids and proteins secreted by alveolar type II epithelial cells, is essential to the mechanism of breathing. It forms a film at the air water interface inside the alveoli where it functions in reducing surface tension, easing breathing and preventing alveolar collapse. A deficiency or dysfunction of lung surfactant results in disorders such as Neonatal Respiratory Distress Syndrome (NRDS) and Acute Respiratory Distress Syndrome (NRDS). Cholesterol, a neutral lipid component of lung surfactant, accounts for 3-10% by weight of healthy native surfactant, but is removed from most FDA approved animal derived replacement surfactants. Moreover, its role in the functioning of lung surfactant is not well understood. Different amounts of cholesterol and SP-B, an essential lung surfactant protein, were added to replacement surfactant from which the original proteins and cholesterol had been removed. To study the biophysical effect of cholesterol on SP-B, a Langmuir Trough, an in vitro model of the breathing cycle, was used to measure surface tensions of the mixtures while a fluorescence microscope recorded changes in film morphology. Cholesterol in small amounts, such as 5 wt %, improved absorption of the surfactant, allowing it to reach lower surface tensions more easily than the same surfactant with no cholesterol. Large amounts of cholesterol, such as 20 wt %, inhibited absorption and prevented the surfactant from reaching the required low surface tensions. The addition of cholesterol also caused significant changes to the morphology of the surfactant film. This suggests that there is an optimum cholesterol concentration for replacement surfactants.