Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Enzyme’s newly discovered role may make it target for arthritis treatment

27.06.2005


Scientists have found a new role for a previously identified enzyme that may make it a target for anti-inflammatory treatments.



The finding by researchers at Washington University School of Medicine in St. Louis shows that an enzyme known as cathepsin G regulates the ability of immune cells known as neutrophils to secrete chemicals that attract other immune cells and start the local inflammatory process. Over time, the excessive accumulation of immune cells can lead to tissue and cartilage damage in joints, causing pain and limiting mobility.

"Cathepsin G affects a very early step in this kind of immune response, so inhibiting it has attractive potential for developers of therapeutics," says senior author Christine T.N. Pham, M.D., assistant professor of medicine and a rheumatologist at Barnes-Jewish Hospital.


The study appears in the June 2005 issue of Immunity.

Cathepsin G, which is made by the neutrophils it regulates, is also an attractive target because it belongs to a class of enzymes known as proteases. One principal type of treatment for HIV, the virus that causes AIDS, inhibits proteases, so scientists who try to block cathepsin G’s role in inflammation will already have an extensive body of research results to refer to.

Pham’s lab uses mouse models of arthritis to study the contributions of proteases and other factors to inflammation and arthritis. One such model involves injecting mice with collagen from calf joints.

"The mice make antibodies to that protein because it’s somewhat foreign, but the antibodies have enough cross-reactivity that they will bind to the mouse’s own cartilage and collagen and initiate an inflammation," Pham explains. "This leads to a condition similar to rheumatoid arthritis in the mice."

Three years ago, Pham’s lab published results showing that mice deficient in cathepsin G and other closely related proteases failed to develop arthritis after the injections. This led them to look for the mechanisms by which these proteases regulate inflammation.

Observations made by Pham’s lab and other groups had linked the earliest stages of inflammation in the animal models to neutrophils, which are a kind of immune system firestarter. They arrive first at sites of injury, infection or irritation and secrete chemicals that bring in secondary waves of other immune attack cells.

"The contributions of the neutrophil weren’t always appreciated by scientists," Pham notes. "When patients come to their doctors with arthritis symptoms, the inflammation typically is so well-established that neutrophils are no longer the predominant cell type."

Animal models of inflammation let scientists watch all stages of the inflammatory process and allowed them to see how important neutrophils are to the early stages of that process.

In the new study, Pham and her colleagues showed that cathepsin G is secreted by neutrophils, binds to the cells’ surface membranes, and affects the rearrangement of integrins, an important group of adhesion compounds on the surface of neutrophils.

"The way these integrins rearrange and cluster on the cell surface can send a signal back into the cell that modifies the cell’s behavior, allowing it to do things like secrete inflammatory factors," Pham explains. "The proteases’ ability to affect integrin rearrangement is dependent on their catalytic activity, and that’s an ability that can be taken away from them."

Pham suspects this class of proteases may also be making significant contributions to other autoimmune and inflammatory conditions besides arthritis. She plans further studies to investigate this possibility. Her lab is also working to determine what molecules cathepsin G is sticking to and interacting with on the surfaces of neutrophils and other cells.

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>