The Properties of Marine Mammal Pulmonary Membranes and their Role in Respiratory Pathologies
Abstract
Marine mammals perform astounding feats of breath-holding diving for long periods of time and appreciable depth. In addition, they are able to arise to the surface at remarkable speed. Diving mammals have compliant lungs that are able to collapse as a mechanism to avoid decompression sickness while in human lung collapse is often associated with respiratory disorders. These diving traits put diving mammals into great risk of contracting respiratory diseases, in particular pneumonia. Pneumonia is an inflammatory condition of the lung that primarily affects alveoli and is the biggest cause of morbidity in bottlenose dolphins. In lungs, the very first barrier against oxygen passage from the alveoli to blood is a lipidic membrane often referred to as pulmonary surfactant. The pulmonary surfactant membrane (PSM) is composed of 90% lipids and 10% proteins and is vital for effective alveoli expansion and contraction. At present, there is a critical knowledge gap between what it known about respiratory diseases and how it relates to the properties of lung tissue, pneumocyte metabolism, and the PSM. This is particularly the case for marine mammals and the development of new therapies hinges on our ability to decipher these basic science concepts. We know that lipid composition changes significantly during respiratory diseases. For example, cardiolipin (CL), which is a mitochondrial-specific phospholipid, is significantly elevated in terrestrial mammalian lungs infected with bacterial pneumonia. However, the effect that CL may have on PSMs remained elusive until very recently. In our ONR-funded work (#N00014161288) we made significant advances to elucidate the effect of pneumonia lipids on PSM integrity. We employed microscopy and spectroscopic techniques on model PSMs as well as bovine extracted PSMs. The main finding is that altering PSM composition with CL induces structural defects; in particular the formation of multiple membrane contacts that also disturb PSM mechanical integrity. Very recently, we also found that CL significantly alters the oxygen permeation profile of model and bovine extracted PSM membranes. In this work, we will elucidate the compositional, structural, mechanical, and gas exchange properties of PSMs from unfit diving mammals and find strategies to restore their function. We propose an innovative approach to underpin pulmonary surfactant activity in conditions that represent the complexity of alveoli tissue. This fundamental research could potentially be channeled towards the development of improved surfactant replacements therapies for respiratory diseases that cannot be successfully treated nowadays. APPROVED FOR PUBLIC RELEASE.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 04, 2020
- Source ID
- N000142112029
Entities
People
- Cecilia Leal
Organizations
- Office of Naval Research
- United States Navy
- University of Illinois Urbana–Champaign