Navigation Links
New immune defense enzyme discovered
Date:4/3/2012

This release is available in German.

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. 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
djenne@neuro.mpg.de
49-898-578-3588
Max-Planck-Gesellschaft
Source:Eurekalert  

Related biology news :

1. Key to immune system disease could lie inside the cheek
2. Immune system implicated in prematurity complication
3. New insight into mechanisms behind autoimmune diseases suggests a potential therapy
4. UCI-led study uncovers how Salmonella avoids the bodys immune response
5. U of Alberta researcher steps closer to understand autoimmune diseases
6. Depression could be evolutionary byproduct of immune system
7. Secrets of immune response illuminated in new study
8. Human immune cells react sensitively to stress
9. Stealthy leprosy pathogen evades critical vitamin D-dependent immune response
10. Aiding cancer therapy by mathematically modeling tumor-immune interactions
11. UCSF team uncovers how immune cells move against invaders
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
New immune defense enzyme discovered
(Date:4/14/2016)... 2016 BioCatch ™, the ... announced the appointment of Eyal Goldwerger as ... Goldwerger,s leadership appointment comes at a time of ... deployment of its platform at several of the world,s ... discerns unique cognitive and physiological factors, is a winner ...
(Date:3/31/2016)... R.I. , March 31, 2016  Genomics firm ... of founding CEO, Barrett Bready , M.D., who ... members of the original technical leadership team, including Chief ... President of Product Development, Steve Nurnberg and Vice President ... returned to the company. Dr. Bready served ...
(Date:3/22/2016)... March 22, 2016 ... Sensors Market for Consumer Industry by Type (Image, ... Application (Communication & IT, Entertainment, Home Appliances, ... Forecast to 2022", published by MarketsandMarkets, the ... to reach USD 26.76 Billion by 2022, ...
Breaking Biology News(10 mins):
(Date:4/29/2016)... 29, 2016 According to ... Research "Separation Systems for Commercial Biotechnology Market - ... Forecast 2015 - 2023", the separation systems for ... Mn in 2014 and is projected to expand ... 2023 to reach US$ 19,227.8 Mn in 2023. ...
(Date:4/29/2016)... ... 29, 2016 , ... Intelligent Implant Systems announced today that the two-level components ... in the United States. These components expand the capabilities of the system and ... beginning in October of 2015, the company has seen significant sales growth in 1Q ...
(Date:4/28/2016)... NEW YORK , April 28, 2016 /PRNewswire/ ... biotechnology acceleration company reports the Company,s CEO  was ... capital titled Accelerators Enter When VCs Fear To ... Life Science Leader magazine is an ... work for everything from emerging biotechs to Big ...
(Date:4/28/2016)... ... April 28, 2016 , ... ... investments in recruiting top industry experts, and expanding its LATAM network and logistics ... tools for clients to manage their clinical trial projects. , The expansion will ...
Breaking Biology Technology: