Pulmonary surfactant is a mixture of lipids and proteins that lines the surface of the lungs to aid in their physiological functions. Abnormalities in the biochemistry of pulmonary surfactant has been observed in a variety of obstructive lung diseases, as well as in pulmonary alveolar proteinosis (PAP). Pulmonary alveolar proteinosis is extremely rare, and involves resident cells in the lungs unable to properly clear the surfactant, minimizing the area available for gas diffusion, and ultimately leading to respiratory failure.
Researchers at the University of Michigan have characterized a novel enzyme, lysosomal phospholipase A2 (LPLA2), which is specifically expressed in the alveolar macrophage. The enzyme recognizes pulmonary surfactant phospholipids as substrates and may play a key role in the degradation of pulmonary surfactant phospholipids. In addition, the researchers have demonstrated that administration of LPLA2 can increase phospholipids catabolism in adipose tissues and inhibit the accumulation of foam cells in the arterial walls of mammals. Therefore, LPLA2 may be used to treat coronary heart disease and atherosclerosis, as well as to PAP. A transgenic animal with a disrupted lpla2 gene has also been developed.
Applications and Advantages
- New treatment for PAP and other-nl-diseases characterized by excess-nl-pulmonary surfactant
- Platform for the screening of potential-nl-drug candidates for phospholipidosis.
- Treatment for coronary heart disease an-nl- atherosclerosis.
- Non-invasive therapeutics for PAP