ELLA MARU STUDIO
Immune system cells are supposed to fight disease. But some may also play an everyday role in helping your heart beat on time. That’s the unexpected finding of a new study.
The immune cells are a type of white blood cells known as macrophages (MAK-roh-FAY-zhuz). They usually protect the body from invading disease-causing microbes. But in mice, at least, they also help electricity flow between heart-muscle cells.
A steady pattern of electrical zaps instruct the heart’s muscle cells each time it should contract. This creates their rhythmic pattern, known as the heartbeat. Those contractions pump blood through the heart and on throughout the rest of the body.
Macrophages squeeze in between heart muscle cells. There, they “plug in” to the muscle cells. Doing so aids the heart cells in receiving the electrical signals they need to stay on beat.
Matthias Nahrendorf is a cell biologist at Harvard Medical School in Boston, Mass. He and his team shared this new discovery April 20 in the journal Cell.
Electrifying find was an accident
Researchers have known for several years that macrophages live in healthy heart tissues. But what they did there was “still very much a mystery,” says Edward Thorp. He’s an immune-system expert at Northwestern University’s Feinberg School of Medicine in Chicago, Ill. He was not involved in the new research.
Nahrendorf was curious about those macrophages in the heart. So he tried to perform an MRI scan on the heart of a mouse that was genetically engineered to not have macrophages in their hearts. The scan wasn't successful. The animal’s heartbeat was too slow and irregular to get a scan.
Those symptoms pointed to where the heartbeat problem likely was. It’s a bundle of muscle fibers known as the atrioventricular (AY-tree-oh-ven-TRIK-u-lur) node. This AV node electrically connects the upper and lower chambers of the heart.
People with AV-node irregularities may need a pacemaker to keep their heart beating as it should. In healthy mice, researchers discovered macrophages concentrated in the AV node. What the cells might be doing there, however, had been unclear.
So Nahrendorf’s team isolated a single heart macrophage and then tested it. It showed no electrical activity. As a result, the mystery remained. Then the researchers linked a macrophage to a heart-muscle cell. The two began communicating electrically. Now an answer to that mystery started to emerge. After all, electrical messages are what stimulate heart-muscle cells to contract.
Chemistry plays a role
Ions are charged molecules. And heart muscle cells have an imbalance of them. While resting, there are more positive ions outside a heart-muscle cell than inside it. When a muscle cell receives an electrical signal from a neighboring heart cell, that distribution of ions switches. Now there are more positive ions inside the cell than outside it. That switch is called a depolarization (De-POH-lur-ih-ZAY-shun).
This brief change causes the cell to contract. And this sends the electrical signal on to tell the neighboring muscle cell to depolarize.
Scientists previously thought that heart-muscle cells could make this ionic shift on their own. But Nahrendorf’s team found that macrophages play a role, too. Using a protein, a macrophage hooks onto a heart-muscle cell. This protein directly connects the inside of these cells to each other. Doing so lets macrophages transfer positive ions — and a positive electric charge. It’s like using that protein as a jumper cable to give the muscle cell a little electrical jumpstart. This makes it easier for the heart cells to depolarize and trigger the heart contraction, Nahrendorf says.
“With the help of the macrophages, the conduction system becomes more reliable,” he says. That means, he adds, “it is able to conduct faster.”
Nahrendorf and his colleagues have found macrophages within the AV node in human hearts, too. They don’t know, however, if these cells play the same role in people. The next step will be to confirm their role. The team also wants to explore whether heart problems such as arrhythmias might be due in part to an absence of macrophages. Or maybe the cells are no longer so good at jumpstarting heart-muscle cells any more.
Thorp at Northwestern calls the study’s conclusion that macrophages electrically work with heart-muscle cells as “paradigm shifting.” By that he means, they could alter our basic understanding of how these cells work. Indeed, Thorp says, the new data highlight the importance of macrophages, beyond their role in defending the body from germs.
arrhythmia An altered and usually erratic pattern in a normal rhythm, such as the pace of an individual’s heartbeats. A persistent, untreated heart arrhythmia can prove very dangerous.
cell The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall. Depending on their size, animals are made of anywhere from thousands to trillions of cells. Some organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.
chemistry The field of science that deals with the composition, structure and properties of substances and how they interact. Chemists use this knowledge to study unfamiliar substances, to reproduce large quantities of useful substances or to design and create new and useful substances.
colleague Someone who works with another; a co-worker or team member.
contract To activate muscle by allowing filaments in the muscle cells to connect. The muscle becomes more rigid as a result.
electric charge The physical property responsible for electric force; it can be negative or positive.
electricity A flow of charge, usually from the movement of negatively charged particles, called electrons.
fiber Something whose shape resembles a thread or filament. (in nutrition) Components of many fibrous plant-based foods. These so-called non-digestible fibers tend to come from cellulose, lignin and pectin — all plant constituents that resist breakdown by the body’s digestive enzymes.
germ Any one-celled microorganism, such as a bacterium or fungal species, or a virus particle. Some germs cause disease. Others can promote the health of more complex organisms, including birds and mammals. The health effects of most germs, however, remain unknown.
immune Able to ward off a particular infection.
immune system The collection of cells and their responses that help the body fight off infections and deal with foreign substances that may provoke allergies.
ion (adj. ionized) An atom or molecule with an electric charge due to the loss or gain of one or more electrons. An ionized gas, or plasma, is where all of the electrons have been separated from their parent atoms.
macrophage A type of white blood cell dispatched by the immune system. Like janitors of the body, they gobble up germs, wastes and debris for disposal. These cells also stimulate other immune cells by exposing them to small bits of the invaders.
microbe Short for microorganism. A living thing that is too small to see with the unaided eye, including bacteria, some fungi and many other organisms such as amoebas. Most consist of a single cell.
molecule An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O2), but water is made of two hydrogen atoms and one oxygen atom (H2O).
magnetic resonance imaging (MRI) An imaging technique to visualize soft, internal organs, like the brain, muscles, heart and cancerous tumors. MRI uses strong magnetic fields to record the activity of individual atoms.
muscle A type of tissue used to produce movement by contracting its cells, known as muscle fibers.
node A person or thing in a network.
pacemaker A small medical device implanted in the body to help control abnormal heart rhythms. This device sends an electrical signal. It stimulates the heart to beat at a regular and healthy rate.
paradigm A totally new idea about or approach to doing, making or thinking about something. For instance, astronomy is described as having undergone a paradigm shift when scientists accepted that the sun — not the Earth — was the center of the solar system.
protein Compounds made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. Among the better-known, stand-alone proteins are the hemoglobin (in blood) and the antibodies (also in blood) that attempt to fight infections. Medicines frequently work by latching onto proteins.
symptom A physical or mental indicator generally regarded to be characteristic of a disease. Sometimes a single symptom — especially a general one, such as fever or pain — can be a sign of any of many different types of injury or disease.
tissue Made of cells, any of the distinct types of materials that make up animals, plants or fungi. Cells within a tissue work as a unit to perform a particular function in living organisms. Different organs of the human body, for instance, often are made from many different types of tissues.