Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New immune defence enzyme discovered

04.04.2012
A previously unknown serine protease forms part of the antibacterial defence arsenal of neutrophil granulocytes

Neutrophil granulocytes comprise important defences for the immune system. When pathogenic bacteria penetrate the body, they are the first on the scene to mobilise other immune cells via signal molecules, thereby containing the risk.


Microscope image of normal human bone marrow tissue with stained NSP4 in myeloblasts and myelocytes. © MPI of Neurobiology

To this end, they release serine proteases – enzymes that cut up other proteins to activate signal molecules. Scientists at the Max Planck Institute of Neurobiology in Martinsried have now discovered a new serine protease: neutrophil serine protease 4, or NSP4. This enzyme could provide a new target for the treatment of diseases that involve an overactive immune system, such as rheumatoid arthritis.

The functioning of the immune system is based on the complex interplay of the most diverse cells and mediators. For example, neutrophil granulocytes (a group of specialized white blood cells) react to bacteria by releasing substances called serine proteases. These enzymes are able to activate signal molecules, such as the chemokines, by cleaving them at a specific position on the molecule. The active signal molecules then guide other immune cells to the focus of inflammation in order to destroy the pathogens.

A research team led by Dieter Jenne at the Max Planck Institute of Neurobiology in Martinsried has come across a previously unknown protease in humans: neutrophil serine protease 4, or NSP4. "The special thing about this enzyme is that it cuts proteins that have the amino acid arginine at a particular point", says Dieter Jenne, research group leader at the Martinsried-based Institute. "This is where NSP4 differs from the other three known neutrophil serine proteases, which are similar in molecular structure, but have a different recognition motif." The scientists may be able to harness this difference to develop an active substance that specifically inhibits NSP4, thereby reducing the immune reaction.

However, serine protease activity comes at a cost. The enzymes not only heal inflammations, but sometimes cause them in the first place. If too many immune cells are activated, they can use their arsenal of aggressive chemical weapons against the body's own tissues. A number of chronic inflammatory diseases are based on precisely this effect. As a result, scientists are searching for substances that can block the neutrophil proteases. To date, however, none of the substances tested have been developed into effective drugs.

"So far, we don't know the identity of the NSP4 substrate, but we assume they must be signal molecules", says Dieter Jenne. Activated chemokines can recruit a vast number of neutrophils, and their sheer quantity alone is enough to cause tissue damage. "Proteases sometimes act as accelerants and can even trigger a chronic inflammation quite independently of bacterial intruders. If we dampened down the defences, we could counteract this effect", explains the scientist.

In terms of evolutionary history, NSP4 is the oldest of the four known neutrophil serine proteases. Using gene sequences, scientists have shown that the enzyme has hardly changed through hundreds of millions of years of evolution from bony fish to humans. "That would indicate that NSP4 regulates a fundamental process", says Dieter Jenne.

The fact that the enzyme remained undiscovered until now is because it occurs at a much lower concentration than the other three proteases. The Max Planck scientists came across it while searching the human genome for genes that encode serine proteases. In the process, they noticed a previously unknown gene sequence. Natascha C. Perera, a member of the Martinsried research group and lead author of the study, managed to produce and examine the enzyme in its active, folded state.

If they are to establish NSP4 in the future as a possible target protein for anti-inflammatory drugs, the scientists must now examine its function in living organisms and discover whether blocking the enzyme has adverse effects. The scientists are working with the company Novartis to answer these questions in laboratory mice. "NSP4 inhibitors could be used in diseases like chronic arthritis or inflammatory skin diseases", says Dieter Jenne, "but first we have to test the long-term effects of these substances."

Contact

Dr. Dieter Jenne
Max Planck Institute of Neurobiology, Martinsried
Phone: +49 89 85783588
Fax: +49 89 89950180
Email: djenne@neuro.mpg.de
Original publication
Perera NC, Schilling O, Kittel H, Back W, Kremmer E, Jenne DE (2012)
NSP4, an elastase-related protease in human neutrophils with arginine specificity

PNAS, April 2, 2012 DOI: 10.1073/pnas.1200470109

Dr. Dieter Jenne | EurekAlert!
Further information:
http://www.mpg.de/5589778/immune_defence_enzyme

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Future electronic components to be printed like newspapers

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...

Im Focus: First evidence on the source of extragalactic particles

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...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

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...

Im Focus: Breaking the bond: To take part or not?

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...

Im Focus: New 2D Spectroscopy Methods

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....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>