Imagine being surrounded by a horde of zombies. Now imagine that miasma invading your nostrils could have the potential to cure several diseases (except the zombie virus, of course).
Zombies may not exist, but putrescine does. This putrid — obviously — substance is released when white blood cells eat dead cells in the body. Corpses aren’t the only things in which the process, called efferocytosis, happens. Dead micro-materials need to be cleaned up in living organisms before inflammation or necrosis can set in. Now, in one of the most unlikely twists you never even saw coming in a horror movie, putrescine has shown its ability to reverse atherosclerosis and other inflammatory illnesses.
“Macrophage metabolism of [dead cell]-derived metabolites allows for optimal continual efferocytosis and resolution of injury,” said Ira Tabas of the Tabas Lab at Columbia University Irving Medical Center, who led a study recently published in Cell Metabolism.
But first, how do rotting cadavers get to smell so rancid? It isn’t completely unlike a ravenous zombie, though zombies usually prefer fresh meat. Macrophages are a type of white blood cell that specifically exist to digest dead cells. Within minutes of cellular death, they start to feast on the dead stuff and ingest amino acids like arginine, which the body uses to make proteins, and ornithine. Efferocytosis gets a boost from the arginase 1 (Arg1) and ornithine decarboxylase (ODC) that macrophages metabolize into putrescine. Putrescine switches on the protein Rac1, which zaps a signal to the macrophages to keep consuming the lifeless cells lying around.
Even in a living human body, about a billion cells die every day. At least the amount of putrescine produced in something alive is way too minimal to smell like eau de corpse.
Atherosclerosis happens when plaque made up of excess fat, cholesterol and other substances in blood which build up in the arteries. Plaque hardens over time and makes it more and more difficult for that oxygen-rich blood to reach the heart. If left untreated, it can blow up into a heart attack or stroke. What might blow your mind even more is that medical use of putrescine could extend beyond atherosclerosis and treat Alzheimer’s and other diseases that result from inflammation.
Tabas and his research team tested how effective macrophages spewing out putrescine could be in the treatment of atherosclerosis in mice. Before actually running tests, they put together human macrophages and dying cells in a petri dish to watch efferocytosis as it happened. This is when they found out that macrophages recycle the amino acids in the dead cells they devour to create putrescine. They also noticed that mice with atherosclerosis didn’t have enough arginase 1 to make putrescine. After those observations, they dissolved it in water, which got rid of the smell, and gave it to the mice with atherosclerosis. They not only drank it without balking, but eventually showed no more signs of illness.
"Of course we do not yet know the feasibility and safety of using low-dose putrescine to ward off atherosclerotic heart disease and other diseases driven by defective efferocytosis," Tabas said. "However, the study shows the potential of treating heart disease with compounds that help macrophages eat dead cells and that are currently in clinical trials for other indications."
Until then, you might want to hold off on that extra slice of pizza.