Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Not even cell death can stop the alarm

23.06.2014

Even after a cell dies, components of the immune system remain active and continue to fuel inflammatory reactions.

An international team of researchers under the direction of scientists from the Institute of Innate Immunity at the University Hospital of Bonn has discovered how this incredible form of communication works.


Image of macrophages containing activated inflammasomes: redistribution of ASC molecules (green) to form ASC specks (green fibrillar structures). Nuclei are shown in blue and plasma membranes in red.

(c) Photo: Eicke Latz/Uni Bonn

The findings offer potentially novel approaches for therapies against many serious diseases that affect a large part of the population, such as gout, atherosclerosis and Alzheimer's disease. The exciting new results are now published in the renowned journal "Nature Immunology".

When there is stress in living immune cells, – for example due to the detection of microbes, or the deposition of uric acid crystals in joints, cholesterol in blood vessels or Alzheimer's plaques in the brain – the so-called ‘inflammasome’ sounds the alarm. Inflammasomes are large multiprotein complexes, which form when they sense cell stress.

The inflammasomes activate an enzyme, which stimulates important messengers that in turn trigger an inflammatory reaction. During this cell activation, the affected immune cells die and thus the inflammatory reaction should come to a halt. "This mechanism primarily protects the body from infections and harmful influences," says Prof. Eicke Latz, the director of the Institute of Innate Immunity at the University Hospital in Bonn.

Strikingly, these new findings reveal that inflammasomes remain active even when the cells have died. The scientists were able to demonstrate that activated inflammasomes also have enzymatic functions outside of the living cell and can thus activate additional messengers. In a type of chain reaction, the inflammasomes released from dying cells are taken up by neighboring immune cells where they can activate more inflammasomes.

This discovery was made by an international team of researchers under the direction of the members from the Institute of Innate Immunity, together with scientists from Hannover Medical School, the University of Massachusetts Medical School (USA), the German Center for Neurodegenerative Diseases (DZNE) in Bonn, the University of Trondheim (Norway), the University of Newcastle (Australia) and the Zurich University Hospital (Switzerland).

Protein complexes shift into defense mode

When the inflammasomes are switched on, within seconds they form functional protein complexes, which can be as large as a bacterium. "In the event of stress or infection, this protein complex forms and provokes the activation of pro-inflammatory messengers within the cell and – as we now know – this can also occur outside of the cell. In this way, there can be a very rapid inflammatory reaction which helps the undesired insult or microbial invaders to be eliminated as quickly as possible," explains lead author Dr. Bernardo S. Franklin, a fellow of the Alexander von Humboldt Foundation working in Prof. Latz's team.

Using fluorescence techniques, the researchers labeled the inflammasome in immune cells. Whenever it was active, it formed a fluorescent protein complex, reminiscent of small stars glowing inside the cell. Using this method, the scientists were able to track the inflammasome after cell death, and show that it remained switched on as an intact protein complex. They also found that once released from the dead cell, it stimulated neighboring cells to undergo an inflammatory reaction. Furthermore, they found that these extracellular complexes accumulate in the lungs of patients with chronic lung disease.

Starting points for new therapies against widespread diseases

"Normally, the immune system is very helpful for averting harmful damage to tissue by initiating an inflammatory reaction," says Prof. Latz. However, if such inflammatory reactions are excessive or if they persist for longer than necessary, this may contribute to common diseases of Western society, such as gout, Alzheimer's disease, diabetes or atherosclerosis. With the discovery of extracellular inflammasomes, the researchers have revealed an interesting avenue for potential new therapies: "If we are able to produce suitable antibodies, it is likely we could contain the alarm of the inflammasome outside of cells and thus keep harmful chronic inflammatory reactions at bay, without affecting the necessary response inside the cell" says Prof. Latz.

Publication: The adaptor ASC has extracellular and prionoid activities that propagate inflammation, "Nature Immunology", DOI: 10.1038/ni.2913

Contact information:

Prof. Dr. Eicke Latz
Institute of Innate Immunity
University Hospital of Bonn
Tel. 0228/28751223
E-Mail: eicke.latz@uni-bonn.de
Web: www.iii.uni-bonn.de

Johannes Seiler | idw - Informationsdienst Wissenschaft

Further reports about: activation death diseases immune inflammatory reaction therapies

More articles from Health and Medicine:

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

nachricht The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>