(218e) Modification of Lung Surfactant Properties Following Contact with Inflammation Products

Acute Respiratory Distress Syndrome (ARDS) begins with inflammation in the lung, which can arise from pneumonia, car accidents, fat embolism, near drowning, and advanced Covid-19 infection. How these conditions progress to ARDS is unknown and there are no generally accepted treatments resulting in a 40% mortality rate. Significant pulmonary inflammation accompanied by reduced blood oxygenation are the common factors in ARDS patients. During inflammation, the concentration of phospholipase A₂ increases in the alveolar fluids and hydrolyzes bacterial and viral phospholipids into more soluble lysolipids, leading to membrane permeabilization and cell lysis. The resulting increased concentration of lysolipids in the alveolar fluid alter the dynamic surface tension and dilatational modulus of the lung surfactant film. Under the continuous area oscillation similar to that during normal breathing, monolayers of dipalmitoyl phosphatidylcholine (DPPC) are solubilized into lysolipid micelles leading to an increase in surface tension and a significant decrease in dilatational modulus on subphases with physiologically relevant concentrations of lysolipid. These changes lead to the Laplace instability in which smaller alveoli have a higher capillary pressure than larger alveoli, potentially leading to alveolar collapse or over-inflation. These changes in dilatational modulus and surface tension only occur for lysolipid concentrations above the critical micelle concentration showing that the presence of lysolipid micelles is essential to removing DPPC from the interface. These findings provide a new mechanism suggesting how the innate immune system may be behind the alveolar collapse and uneven lung inflation during ARDS.