Verification of Proposed Mechanism Causing Acute Respiratory Distress Syndrome via Solubilization of Dipalmitoylphosphatidylcholine into Lysolipid Micelles.
Acute Respiratory Distress Syndrome, known as ARDS, is a form of lung injury characterized by poor oxygenation and non-compliant lungs. It usually follows a traumatic event, manifesting as severe progressive hypoxemia, as the lungs are unable to provide oxygen to the blood. This is due to increased surface tension caused by the breakdown of dipalmitoylphosphatidylcholine (DPPC), the primary lipid in lung surfactant, by phospholipase A2 (PLA2), an enzyme that accompanies lung inflammation. The breakdown of DPPC forms another surfactant known as lysophosphatidylcholine (LysoPC), which is less effective at lowering the surface tension of an interface. I hypothesize that when a lysolipid is present above the critical micelle concentration, the lysolipid micelles can solubilize healthy lung surfactant from the liquid-air interface, then replace the healthy surfactant at the interface. To test this, samples of DPPC and LPG were analyzed using pulsed field gradient nuclear magnetic resonance (PFG-NMR) to determine the diffusion coefficients of each species. Species with similar diffusion coefficients can be assumed to be in the same complexes. Preliminary results show that DPPC and LPG share a diffusion coefficients around 1.7 * 10-11 m2/s, indicating they are present in structures together. In this way, it can be determined if lysolipid micelles are able to solubilize healthy lung surfactant from the liquid-air interface. These findings provide more insight into the mechanisms and progression of ARDS, and enable future study into a potential clinical solution in lysolipids.