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How to Feed a Macrophage

Posted on by Lawrence Tabak, D.D.S., Ph.D.

Dark light microscopy with man small circles. Green macrophages are nearly filled with some of the circles.
Credit: Annalise Bond, Morrissey Lab, University of California, Santa Barbara

For Annalise Bond, a graduate student in the lab of Meghan Morrissey, University of California, Santa Barbara (UCSB), macrophages are “the professional eaters of our immune system.” Every minute of every day, macrophages somewhere in the body are gorging themselves to remove the cellular debris that builds up in our tissues and organs.

In this image, Bond caught several macrophages (green) doing what they do best: shoveling it in—in this case, during a lab experiment. The macrophages are consuming silica beads (purple) prepared with biochemicals that whet their appetites. Each bead measures about five microns in diameter. That’s roughly the size of a bacterium or a spent red blood cell—debris that a macrophage routinely consumes.

When Bond snapped this image, she noticed a pattern that reminded her of a childhood tabletop game called Hungry Hungry Hippos. Kids press a lever attached to the mouth of a plastic hippo, its lower jaw flaps open, and the challenge is to fill the mouth with as many marbles as possible . . . just like the macrophages eating beads.

Bond adjusted the colors in the photo to make them pop. She then entered it into UCSB’s 2023 Art of Science contest with the caption of Hungry Hungry Macrophages, winning high marks for drawing the association.

Though the caption was written in fun, Bond studies in earnest a fascinating biological question: How do macrophages know what to eat in the body and what to leave untouched?

In her studies, Bond coats the silica beads shown above with a lipid bilayer to mimic a cell membrane. To that coating, she adds various small molecules and proteins as “eat-me” signals often found on the surface of dying cells. Some of the signals are well characterized; but many aren’t, meaning there’s still a lot to learn about what makes a macrophage “particularly hungry” and what makes a particular target cell “extra tasty.”

Capturing fluorescent images of macrophages under the microscope, Bond counts up how many beads are eaten. Beads bearing no signal to stimulate their appetite might get eaten occasionally. But when an especially enticing signal is added, macrophages will gorge themselves until they can’t eat anymore.

In the experiment pictured above, the beads contain the antibody immunoglobulin G (IgG), which tags foreign pathogens for macrophage removal. Interestingly, IgG antibody responses also play an important role in cancer immunotherapies, in which the immune system is unleashed to fight cancer.

Among its many areas of study, the NIH-supported Morrissey lab’s wants to understand better how macrophages interact with cancer cells. They want to learn how to make cancer cells even tastier to macrophages and program their elimination from the body. Sorting out the signals will be challenging, but we know that macrophages will take a bite at the right ones. They are, after all, professional eaters.


Cancer Immunotherapy (NIH)

Annalise Bond (University of California, Santa Barbara)

Morrissey Lab (University of California, Santa Barbara)

Art of Science (University of California, Santa Barbara)

NIH Support: National Institute of General Medical Sciences

Snapshots of Life: A Flare for the Dramatic

Posted on by Dr. Francis Collins

lipid-covered water drop

Credit: Valentin Romanov, University of Utah, Salt Lake City

Oil and water may not mix, but under the right conditions—like those in the photo above—it can sure produce some interesting science that resembles art. You’re looking at a water droplet suspended in an emulsion of olive oil (black and purple) and lipids, molecules that serve as the building blocks of cell membranes. Each lipid has been tagged with a red fluorescent marker, and what look like red and yellow flames are the markers reacting to a beam of UV light. Their glow shows the lipids sticking to the surface of the water droplet, which will soon engulf the droplet to form a single lipid bilayer, which can later be transformed into a lipid bilayer that closely resembles a cell membrane. Scientists use these bubbles, called liposomes, as artificial cells for a variety of research purposes.

In this case, the purpose is structural biology studies. Valentin Romanov, the graduate student at the University of Utah, Salt Lake City, who snapped the image, creates liposomes to study proteins that help cells multiply. By encapsulating and letting the proteins interact with lipids in the artificial cell membrane, Romanov and his colleagues in the NIH-supported labs of Bruce Gale at the University of Utah and Adam Frost at the University of California, San Francisco, can freeze and capture their changing 3D structures at various points in the cell division process with high-resolution imaging techniques. These snapshots will help the researchers to understand in finer detail how the proteins work and perhaps to design drugs to manipulate their functions.