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JUST THE FAQs: Why Do Macrophages Do What They Do?

A new study led by Christopher K. Glass, MD, PhD, UC San Diego School of Medicine professor, answers longstanding questions about what makes a macrophage the sort of macrophage it is.

What are macrophages and what do they do?

Macrophages are a type of immune cell. They respond to infections and injuries in the human body. Macrophages are found in all tissues of the body, where they are best known for engulfing invading pathogens and cleaning up damaged tissue. But on top of that, macrophages also take on specialized roles that serve the needs of their own home tissues. For example, macrophages in the brain (called microglia) remove toxic protein aggregates and develop the ability to “prune” extra connections between neurons. Meanwhile, macrophages in the peritoneum, the body cavity surrounding the large and small intestines, secrete factors that control the functions of other immune cells.

How do tissue macrophages attain their specialized functions?

Before this study, not much was known about how macrophages in each tissue attain their specialized functions. It also wasn’t well understood how some macrophages turn on one set of genes while others use different genes to perform their specialized duties.

But now Glass and his team have made two important discoveries. The first is that the peritoneum and the brain send out different “instructions” (soluble factors) that tell their local macrophage populations where they are and what they should do. And these instructions are constantly required to maintain the distinct “personalities” of microglia and peritoneal macrophages. If the macrophages are removed from their normal environments and placed into culture, they lose many of the distinguishing features they normally have in living systems.

The second major discovery has to do with macrophage gene regulation. The turning off and on of genes is controlled by special regions of the genome called enhancers. These are short DNA segments that don’t code for proteins but instead have the potential to activate nearby genes. This study provides insights into how different tissue environments (such as in the brain vs. the peritoneum) direct specific patterns of gene expression via enhancers.

What could this study mean for human health?

Most human genetic variation associated with disease is in regions of the genome that don’t code for proteins. This study indicates how non-coding mutations could affect enhancers that are required for the specific functions of macrophages and microglia in common human diseases, such as diabetes and neurodegenerative diseases. These findings provide important general insights into understanding how such genetic variation can affect disease risk in humans.

To learn more read the paper, published Dec. 4 by Cell.

Pictured: A scanning electron micrograph of a false-colored macrophage digesting a bit of debris. Image courtesy of Steve Gschmeissner.

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An open question to anyone who has been to a hospital:

Most of us have been to a hospital at some points in our lives and some of us spend more time there than we would like. If you ask the average person, they will tell you that a hospital is not an enjoyable place to be, and that’s a shame. Here’s a quick primer (or reminder) as to what it might look like to be bound to a hospital bed:

For those of you who have been in that position, do any simple changes spring to mind which, if put in place, would lead to a better stay?

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Cell cleavage in the early embryo.

Starting with this process, the fertilised human ovum goes from a lone cell, to two, to four, to eight, to sixteen…

…to a whole human being.

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Above: the tip of a hypodermic syringe.

Below: the tip of a fang from the cobra Naja kaouthia.

Both are designed to pierce the skin and admit fluids into the bloodstream, although it is often the case that the intended effects are polar opposites.

Artificial designs frequently imitate those of nature; in this case, mankind was approximately 25 million years late. 

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 “Technological mandala 02″ by Leonardo Ulian,

aesthetics of electric components

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Lichtenberg figures on skin, colloquially known as lightning flowers.

These dramatic scars occur when lightning or other high-energy electrical arcs strike the body. The arc conducts beneath the skin, bursting subcutaneous capillaries and forming there these densely branched patterns in its wake. 

When performed intentionally under controlled conditions, the same phenomena can instead form beautiful 'captured lightning.'

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Heartbeats under magnetic resonance imaging.

We seldom consider the force with which our hearts beat through every moment of our lives. Most of us will only ever feel the dampened strength of these muscles at the arteries of the wrist or neck, perhaps through a stethoscope or in moments of excitement, exertion and fear. Take a moment to consider it now, if you will. 

Credit to the VCU Medical Center for these images.

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NASA, Six Photos of an AES Flexibility Test, (1960’s)

These photos show some of the behind the scenes testing that was underway in the U.S. during the space race in the 1960s.

Black and white pictures compiled by San Diego Air And Space Museum show Bill Elkins, a chief engineer at Garrett AiResearch, testing an Advanced Extravehicular Suit (AES), a long-endurance lunar suit he developed for astronauts to wear to the moon.

Though Elkins’ creation beat out four other space suit manufacturers to secure a contact with NASA, his suit never ended up going to space because NASA cancelled all moon landings after Apollo 17 in December 1972. 

"The AES was the first suit to tackle the issues of mobility in space. It had about 95 percent of nude mobility range and had a significantly greater life cycle capability. I don’t remember, but I believe the target length for a lunar stay was about eight days."

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Retinæ as seen through fluorescein angiogram.

The innermost wall of the interior of the eye is lined with the photosensitive cells of the retina.  These images visualize the blood vessels which supply these cells and make vision possible. Originating from the blind spot around the optic disc, these vessels seem to converge upon the dark region at the center. This is the macula lutea, which contains the densely-packed cells responsible for the human eye’s greatest visual potential and your sharpest vision.

If you attempt to read this post at the corner of your eye, you will find it entirely impossible; the parts of the retina responsible for peripheral vision simply lack the resolution for such tasks. 

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An exploded view of the bones of the skull from Intermediate anatomy, physiology and hygiene (1887) by J.C. and C. Cutter. Though it is easy to think of the cranium as a single hollow bone, this is not in fact the case. Indeed, at one point in your life, these bones existed as entirely separate, independent structures.

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In Space and Energy Luca Zanier photographs the insides of nuclear power plants. 

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Thomas Eakins - The Gross Clinic (1875) oil on canvas Something a little different today: this painting carries immense insight into the theater of pre-aseptic surgery. Pictured, a patient undergoes treatment for osteomyelitis of the femur with a conservative approach; the days of total amputation of the limb for the same disease were not far gone.  In contrast to today’s surgical setting, the theater is open to a great many students, who watch from the stands, and a woman presumed to be a member of family. The titular doctor Gross and company would not have necessarily washed their hands or instruments before performing the operation, as was common at the time. The painting represents a transitional period for surgery: the patient was anesthetized and not about to lose a leg on account of his disease, but was likely to suffer infection soon afterwards due to a lack of understanding as to the importance of clinical cleanliness. 

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Electron micrography of bacteriophages and schematic drawing.

Bacteriophages are a diverse group of viruses capable of attacking and infecting bacterial cells. The bulbous but curiously geometric head of the organism contains a DNA payload, which encodes the genome of the virus. 

After alighting on a bacterial cell membrane of a specific target species (pictured, uppermost), the bacteriophage contracts its insectoid tail fibers, and delivers the strand of DNA through the membrane of the host in a manner akin to a 100-nanometer-long, spindly-legged hypodermic syringe. The newly injected DNA inside the host may then propagate further virions, continuing the cycle of the virus; the assembly of an entirely new bacteriophage virion can take as little as 15 minutes within the host.

Some species then explosively release the new virions from the cell, whilst others employ a further-reaching technique: their DNA seamlessly integrates with that of the bacterium fairly harmlessly, until the host begins to die of its own accord. At this stage, the dormant phage DNA initiates the same process described above, with a key difference: any offspring of the original bacterium that it may have produced during its healthy lifespan are also infected with bacteriophage DNA, and will ultimately meet the same demise.

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5mm Embryo appears as Carnegie Stage 13 from ectopic pregnancy.

Embryo is enclosed in amniotic membrane.

Larger cavity is chorionic space (coelom).

Placental villi are visible on left of image.

UNSW Embryology

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Oskar Garvens (1874-1951) - Le Repentir

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cloud iridescence — caused as light diffracts through tiny ice crystals or water droplets of uniform size, usually in lenticular clouds — photographed by rolf kohl. (more cloud pics)