Process suggests a new type of immunotherapy
A team of researchers has devised a Pac-Man-style power pellet that gets normally mild-mannered cells to gobble up their undesirable neighbors. The development may point the way to therapies that enlist patients’ own cells to better fend off infection and even cancer, the researchers say.
Credit: Toru Komatsu/University of Tokyo
Caption: A healthy cell (green) that has recognized and engulfed dying cells (purple).
A description of the work will be published July 15 in the journal Science Signaling.
“Our goal is to build artificial cells programmed to eat up dangerous junk in the body, which could be anything from bacteria to the amyloid-beta plaques that cause Alzheimer’s to the body’s own rogue cancer cells,” says Takanari Inoue, Ph.D., an associate professor of cell biology in the Johns Hopkins University School of Medicine’s Institute for Basic Biomedical Sciences, who led the study. “By figuring out how to get normally inert cells to recognize and engulf dying cells, we’ve taken an important step in that direction.”
Identifying and devouring dying cells and other “junk” is usually the job of white blood cells called macrophages and neutrophils, which also go after bacteria and other invaders in a process called phagocytosis. For the new experiments, Inoue teamed up with researchers at the University of Tokyo to strip down phagocytosis, figuring out the minimum tools one cell needs to eat another one.
They started not with macrophages, but with a type of laboratory-grown human cells known as HeLa, which normally can’t perform phagocytosis. Their first task was to induce the HeLa cells to attach to nearby dying cells by getting the right “receptors” to the HeLa cells’ surface. The researchers knew that part of a receptor protein called MFG-E8 would recognize and stick to a distress signal on the surface of dying cells, and coaxing the HeLa cells to make the protein fragment was straightforward. To get the fragment, termed C2, onto the outside of the cells, the team found a way to stick it to another protein that was bound for the cell’s surface, thus taking advantage of the cell’s own transportation system. “We put C2 on the same bus as the membrane protein,” Inoue says.
As a result, up to six dying cells stuck to each HeLa cell. The bad news was that though they were cozy, the HeLa cells weren’t actually eating the dying cells.
Fortunately, Inoue says, the team already had an idea about what to try next: Other research had shown that activating a gene called Rac would cause a cell to engulf beads stuck to its surface. Sure enough, HeLa cells with both surface C2 and activated Rac swallowed dying cells readily, the team found.
“We’ve shown it’s possible to endow ordinary cells with the power to do something unique: take on the role of a specialized macrophage,” Inoue says.
Inoue cautions that the investigators don’t believe the engulfed cells are being broken down. Getting the HeLa cells to finish the phagocytosis process will be one of the group’s next steps.
Other authors on the paper are Hiroki Onuma, Toru Komatsu, Makoto Arita, Kenjiro Hanaoka, Tasuku Ueno, Takuya Terai and Tetsuo Nagano of the University of Tokyo.
This study was funded by the Ministry of Education, Culture, Sports, Science and Technology of Japan (grant numbers 22000006 and 24655147), the Japan Science and Technology Agency (grant numbers 10602 and 10216), the Mochida Memorial Foundation for Medical and Pharmaceutical Research and the National Institute of General Medical Sciences (grant number GM092930).
Shawna Williams | newswise
'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology
Microfluidics probe 'cholesterol' of the oil industry
23.10.2017 | Rice University
Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
23.10.2017 | Event News
17.10.2017 | Event News
10.10.2017 | Event News
23.10.2017 | Life Sciences
23.10.2017 | Physics and Astronomy
23.10.2017 | Health and Medicine