The heart contains two distinct populations of white blood cells
Confirmation that intruder-gobbling cells have different ancestries and functions fuels search for new therapies. Geetanjali Rangnekar reports.
Researchers have shown that two genetically and functionally distinct types of macrophage —white blood cells that engulf foreign matter — exist in the human heart.
The discovery, by a team led Geetika Bajpai from Washington University in Missouri, US, is revealed in a paper published in the journal Nature Medicine. It has important implications for the development of targeted immune treatments for patients with a particularly insidious type of heart disease.
Macrophages are the mammoth cells that detect, hoover up and destroy microbes and other invaders. The cells are not uniform, however, and are classified into subtypes. Two – dubbed CCR2-plus and CCR2-minus – were identified in mouse hearts in the 1960s, and have been exhaustively researched ever since.
Different macrophage subtypes have previously been found in human organs, including the skin, lungs and eyes, but this is the first study to prove that CCR2-plus and CCR2-minus are found in the human heart.
They were located in samples taken from the left heart chamber of patients with two kinds of cardiomyopathy (CM). This is a condition in which the heart muscle becomes stretched thin and cannot function, leading to heart failure. The only plausible treatments are the insertion of a device into the heart to help it function, or getting a new ticker altogether.
CM has previously been studied in mouse models, where it was found that the CCR2-plus subtype played a role in the destructive inflammatory changes associated with the disease. This led Bajpai and colleagues to investigate the role of these macrophages in patients with CM.
The interesting finding was that the CCR2-plus and CCR2-minus types had different ‘lineages’. CCR2-minus cells descend from cells that are part of a membrane that surrounds the embryo. They migrate to the heart during early stages of human development, and maintain residence there.
CCR2-plus macrophages, much like other blood cells, are produced in bone marrow, originate from cells called monocytes, and are continually drawn into the heart.
These differing origins also mean that the cell sub-types show an individual genetic makeup, which, the authors found, translated into specific functions within the heart.
They found that the CCR2-minus cells were the orchestrators of cardiac repair, rebuilding and regeneration, making them the watchful soldiers, ready to pounce if anything goes awry.
On the other hand, the CCR2-plus cells play a rather damaging role by catalysing inflammation reactions in heart tissue. In fact, the team found an abundance of them around non-viable scar tissue. However, numbers reduced in a subset of patients who recovered functionality in the left chamber of their heart after having an assist device implanted.
The authors found the characteristics of human macrophages to be analogous to the well-defined functions and genetic make-up of those established in mice, providing the first evidence that the subtypes play a role in bringing about heart failure in humans.
This, according to the team, could mean novel targets for developing therapies that take aim at the inflammation-inducing CCR2-plus macrophages.