Office of Technology Transfer – University of Michigan

Lysosomal Phospholipase A2 for Surfactant Metabolism

Technology #2751

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Categories
Researchers
James A. Shayman
Managed By
Ed Pagani
Associate Director, Health Technologies 734-763-3558
Patent Protection
US Patent Pending
US Patent Pending
Publications
The acylation of lipophilic alcohols by lysosomal phospholipase A(2)
JOURNAL OF LIPID RESEARCH, Volume 48. Page 2255. 2007
Positional specificity of lysosomal phospholipase A(2)
JOURNAL OF LIPID RESEARCH, Volume 47. Page 2268. 2006
Lysosomal phospholipase A2 is selectively expressed in alveolar macrophages.
J. Biol. Chem., Volume 41. Page 42605. 2004

Background

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.

Technology

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

Applications

  • 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.

Advantages

  • Non-invasive therapeutics for PAP