Navigation Links
Study finds adult stem cells can replicate

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.

###

Raptis SZ, Shapiro SD, Simmons PM, Cheng AM, Pham CTN. Serine protease Cathepsin G regulates adhesion-dependent ne utrophil effector functions by modulation integrin clustering. Immunity, June 7, 2005, 679-691. Funding from the Arthritis Foundation and the National Institutes of Health supported this research.


'"/>

Source:Children's Hospital of Pittsburgh


Related biology news :

1. Novel Asthma Study Shows Multiple Genetic Input Required; Single-gene Solution Shot Down
2. Emory Study Tests Bone Marrow Stem Cells to Improve Circulation in Legs
3. UCLA Study Shows One-Third of Drug Ads in Medical Journals Do Not Contain References Supporting Medical Claims
4. Study Demonstrates Gene Expression Microarrays are Comparable and Reproducible
5. Study Links Ebola Outbreaks To Animal Carcasses
6. Breakthrough Microarray-based Technology for the Study of Cancer
7. NYU Study Reveals How Brains Immune System Fights Viral Encephalitis
8. Study finds more than one-third of human genome regulated by RNA
9. Leukemia Drug Breakthrough Study In New England Journal Of Medicine
10. Study identifies predictors of HIV drug resistance in patients beginning triple therapy
11. New Study from Affymetrix Laboratories Points to Changing View of How Genome Works
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/1/2016)... 1, 2016  Today, the first day of American ... to develop a first of its kind workplace health ... Watson. In the first application of Watson ... IBM ), and Welltok will create a new offering ... cognitive analytics, delivered on Welltok,s health optimization platform. The ...
(Date:1/25/2016)... BELL, Pa. , Jan. 25, 2016   Unisys Corporation ... recognition system at John F. Kennedy (JFK) International Airport, ... Border Protection (CBP) identify imposters attempting to enter ... do not belong to them. pilot testing of ... out initially at three terminals at JFK during January 2016. ...
(Date:1/21/2016)... January 21, 2016 ... new market research report "Emotion Detection and Recognition Market by ... Tools (Facial Expression, Voice Recognition and Others), Services, ... forecast to 2020", published by MarketsandMarkets, the global ... reach USD 22.65 Billion by 2020, at a ...
Breaking Biology News(10 mins):
(Date:2/5/2016)... MANASSAS, Va. , Feb. 5, 2016 ... organization, is poised to assist the medical and life ... concerns around Zika Virus infection.   CDC ... --> Zika virus is a single-stranded ... also includes the West Nile, Dengue and Chikungunya Viruses. ...
(Date:2/4/2016)... San Francisco, CA (PRWEB) , ... February 04, ... ... future of enterprise talent development and compliance training, today announced an interactive ... on Morf Playbook™. The RAPS (Regulatory Affairs Professional Society) accredited interactive course ...
(Date:2/4/2016)... , Feb. 4, 2016 Beike Biotechnology, ... various medical institutions attended a ceremony in late 2015 ... personalized cell therapy in 2016. --> ... Clinical Translation Platform for Personalized Cell Therapy" was hosted ... Cell Production Center, both subsidiaries of Beike Biotechnology Co., ...
(Date:2/4/2016)... 2016  Spherix Incorporated (Nasdaq: SPEX ) -- an intellectual ... of intellectual property, today provided an update on the ... District of Texas and announcing ... Inter Partes Re-examination ("IPR") proceedings that VTech and ... was initiated on only certain claims of two of ...
Breaking Biology Technology: