Researchers have discovered the way that red blood cell particles interact with white blood cells called macrophages to reduce inflammation and the formation of fatty deposits on arterial walls. They say their findings offer a potential treatment for this common condition, which can result in heart attack and stroke.
The principal way oxygen is delivered from the lungs to the body’s tissues is by red blood cells (RBCs). These cells naturally produce particles called extracellular vesicles (RBCEVs) during cellular aging, disease states, and in response to environmental stressors. RBCEVs protect RBCs by clearing away dangerous molecules, affecting immune cells, and are involved in the inflammatory process.
Atherosclerosis, the build-up of fats, cholesterol and other substances in and on arterial walls, is a common condition that can lead to heart attack, stroke, aneurysm or blood clot. Macrophages, white blood cells considered the ‘first responders’ of the immune system, play a central role in atherosclerosis by ingesting and accumulating lipids, transforming them into foam cells that contribute to and sustain the growth of fatty arterial plaques.
Led by researchers from the National University of Singapore a new study has examined the interaction between RBCEVs and macrophages in hopes of discovering a way of stopping atherosclerosis.
Macrophages often ingest dying cells by recognizing a lipid known as phosphatidylserine (PS) on their cell membranes. Since RBCEVs have an abundance of PS on their membrane, the researchers tested to see if it mediated the uptake of RBCEVs by macrophages. They found that RBCEV uptake by macrophages was very efficient but that when PS receptors on macrophages were blocked, uptake was considerably reduced.
Following the uptake of RBCEVs, the macrophages had decreased levels of pro-inflammatory proteins and produced higher levels of an enzyme that protects cells against oxidative damage often seen in inflammatory and cardiovascular disease. Importantly, the RBCEVs made the macrophages resistant to transforming into foam cells.
The study’s findings suggest that RBCEVs have potential use in alleviating conditions associated with excessive inflammation and treating atherosclerosis, particularly given that RBCEVs are capable of being engineered and loaded with drugs.
“We have known for a while that RBCEVs tend to go to macrophages when they enter the body, but we did not realize some of the implications until now,” said Minh Le, the study’s corresponding author. “The properties of RBCEVs that we have uncovered here are desirable for treating atherosclerosis and possibly other inflammatory diseases.”
Further studies into the effects of RBCEVs using animal models of atherosclerosis will likely advance the development of this therapeutic platform, the researchers say.
The study was published in the Journal of Extracellular Vesicles.