Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Antibody to a naturally-occurring sugar chain in colon inhibits inflammatory bowel disease

10.10.2005


Ensemble of usual sugars offers clues to controlling inflammation



A collaboration led by the Burnham Institute for Medical Research has found that an antibody which binds to an unusual sugar molecule residing in the gut halts the inflammation seen in Crohn’s disease and other intestinal inflammations. The antibody could prove to be a promising drug target for these common chronic intestinal disorders.

Professor Hudson Freeze, Ph.D., director of Burnham’s glycobiology and carbohydrate chemistry program, together with staff scientist Geetha Srikrishna, Ph.D., and other colleagues found that a naturally "tweaked" sugar chain normally present on white blood cells and intestinal cells plays a role in inflammation. In addition, the team found that an antibody produced in reaction to the sugar’s presence curbed intestinal inflammation induced in mice. These findings will be published in the October 15th edition of Journal of Immunology.


"We looked at a number of sugar-binding molecules that may have had a role in inflammation," said Freeze. "One of the sugar chains elicited an antibody response, so we wondered whether the antibody would be able to block inflammation in mice. If so, this could have implications for inflammatory bowel disease, Crohn’s, and also might help combat other autoimmune inflammatory diseases, like arthritis."

The team identified a modified version of very common sugars known as N-linked glycans, which are found on the surface of white blood cells, as well as normal colon cells. These sugars are also found in colon tissue of patients suffering from Crohn’s disease.

The antibody was tested in a mouse model for Crohn’s disease created by transferring white blood cells with the capacity to induce severe intestinal inflammation into mice with compromised immune systems. "When administered 10 days after disease onset, the antibody was able to reverse early symptoms of inflammation and halt further progress of disease," said Srikrishna. The antibody also reduced the accumulation of white blood cells armed to fight disease and inhibited the expression of cellular messengers (cytokines) typically seen in inflammation.

"There are a large number of signaling molecules that are activated in inflammation," said Freeze. "Antibodies against these sugar chain molecules, however, appear to curb inflammation before cytokines associated with inflammation, like NF-kB and TNF, are activated. The sugar chain must be used at an earlier stage, but in a more specific manner."

The sugar chain’s specificity could be crucial to developing treatments for Crohn’s and other inflammatory disorders. The body’s inflammation response usually is a healthy reaction to harmful foreign agents; inflammation disposes of pathogens before they cause disease. Crohn’s disease and other inflammatory bowel diseases, generally known as auto-immune disorders, are a result of the body’s immune system overreacting to non-existent pathogens, causing the body to attack its own tissues. The optimal treatment would inhibit excessive inflammation linked with disease, leaving normal immune function unaffected.

The antibody, Freeze suggests, could prove to be an effective remedy for autoimmune disorders if it can act specifically on hyperactive inflammation, while preserving the immune system. RemicadeTM, an antibody-based drug currently used for Crohn’s, works by inhibiting the cytokines that are summoned into action at a later phase of these diseases.

"Our next step is to identify the molecular players in the body’s early inflammatory response in the intestine," said Freeze. The team is focusing on one particular molecule called RAGE (short for Receptor for Advanced Glycation End Products), which has been implicated in the pathology of inflammation, as well as cancer, diabetes and Alzheimer’s disease. They are also determining the exact molecular structure of the tweaked sugar chain, and will determine what other molecules and receptors may interact with it.

Eventually, the researchers hope that they will have enough promising information to merit a clinical trial to test the antibody’s effectiveness. "Our antibody was developed for use in mice. We need to "humanize" it, make the antibody suitable for human consumption. This could take some development, but the results could be very beneficial," Freeze said.

Freeze’s and Srikrishna’s colleagues included Professor Mitchell Kronenberg, Olga Turovskaya and Raziya Shaikh of the La Jolla Institute for Allergy and Immunology, Robbin Newlin of Burnham, Dirk Foell of the University of Muenster, Germany, and Simon Murch of the University of Warwick, England. The team’s research is supported by grants from the Broad Medical Research Program of The Eli and Edythe L. Broad Foundation and the National Institutes of Health.

Nancy Beddingfield | EurekAlert!
Further information:
http://www.burnham.org

More articles from Life Sciences:

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Underwater acoustic localization of marine mammals and vehicles

23.11.2017 | Information Technology

Enhancing the quantum sensing capabilities of diamond

23.11.2017 | Physics and Astronomy

Meadows beat out shrubs when it comes to storing carbon

23.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>