A receptor on macrophages can detect excessive cell death and recruit help
A receptor, induced on the surface of macrophages under stressful conditions, can detect tissue injury, stimulating inflammation and possibly repair, a RIKEN-led team of molecular biologists has discovered. Their work could provide new leads for anti-inflammatory drugs and healing.
Stress, age and body maintenance generate a continuous supply of dead cells, which normally are cleaned up by the macrophages that engulf pathogens and cellular debris. This mechanism, however, becomes overwhelmed at times of large-scale tissue damage, such as that caused by radiation or injury. To deal with such emergencies, the body needs a sensor which not only can detect the scale of the problem, but also that the dead tissue is not foreign.
Earlier research by another group had suggested that cellular stress leads to an upsurge in the activity of a gene, Mincle, which codes for a surface receptor in macrophages. So the RIKEN-led research team investigated the function of this receptor further. Their findings were published recently in Nature Immunology (1).
Initially, the researchers found that the Mincle receptor is associated with another signaling receptor chain, FcRã and triggers macrophage activation through a specific sequence known as the immunoreceptor tyrosine-based activation motif (ITAM). This stimulates the release of cellular hormones—cytokines and chemokines—that summon neutrophils to take part in inflammation and possibly tissue repair. Using a system involving green fluorescent protein to detect ITAM-mediated cell activation, the researchers found that Mincle responds to the presence of dead cells.
They then purified protein material from dead cells bound to the Mincle receptor, and discovered it was SAP130, a protein found in cell nuclei. SAP130 is released from cells where it can come into contact with the Mincle receptor only after they die and break down. In further experiments, the researchers determined the Mincle alert system works in mammals by showing that in living mice in which thymus cells had been killed by irradiation, the recruitment of neutrophils to the site of the damage was prevented by Mincle-specific antibody.
According to the team leader, Takashi Saito of the RIKEN Center for Allergy and Immunology in Yokohama, the research group now wants to determine the role of the alert system in diseases involving tissue damage; how activation of Mincle is related to the induction of autoimmune diseases such as rheumatoid arthritis; and whether it is possible to inhibit or cure inflammation and/or autoimmune diseases by blocking Mincle.
1. Yamasaki, S., Ishikawa, E., Sakuma, M., Hara, H., Ogata, K. & Saito, T. Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nature Immunology 9, 1179–1188 (2008).
The corresponding author for this highlight is based at the RIKEN Laboratory for Cell Signaling
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences