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
Discovery of a fundamental limit to the evolution of the genetic code
03.05.2016 | Institute for Research in Biomedicine (IRB Barcelona)
03.05.2016 | Christian-Albrechts-Universität zu Kiel
Using an ultra fast-scanning atomic force microscope, a team of researchers from the University of Basel has filmed “living” nuclear pore complexes at work for the first time. Nuclear pores are molecular machines that control the traffic entering or exiting the cell nucleus. In their article published in Nature Nanotechnology, the researchers explain how the passage of unwanted molecules is prevented by rapidly moving molecular “tentacles” inside the pore.
Using high-speed AFM, Roderick Lim, Argovia Professor at the Biozentrum and the Swiss Nanoscience Institute of the University of Basel, has not only directly...
If a person pushes a broken-down car alone, there is a certain effect. If another person helps, the result is the sum of their efforts. If two micro-particles are pushing another microparticle, however, the resulting effect may not necessarily be the sum their efforts. A recent study published in Nature Communications, measured this odd effect that scientists call “many body.”
In the microscopic world, where the modern miniaturized machines at the new frontiers of technology operate, as long as we are in the presence of two...
Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.
Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...
Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.
In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...
Honeycomb structures as the basic building block for industrial applications presented using holo pyramid
Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...
27.04.2016 | Event News
15.04.2016 | Event News
12.04.2016 | Event News
04.05.2016 | Earth Sciences
04.05.2016 | Health and Medicine
03.05.2016 | Physics and Astronomy