Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Preventing toxic side effects of inflammatory disease therapy

10.02.2006


Researchers at the University of California, San Diego (UCSD) School of Medicine have developed a mouse model that could help scientists develop better drugs to fight autoimmune and inflammatory disorders such as multiple sclerosis and rheumatoid arthritis.



Inflammation is a process by which the white blood cells and chemicals of the immune system rally to protect the body from infection and foreign substances such as bacteria and viruses. In autoimmune diseases, however, this defense system triggers an inflammatory response when there are no foreign substances to fight off, or the defense system goes into "overdrive" and forgets how to turn off. In these diseases, the body’s normally protective immune system attacks and damages its own healthy tissues.

UCSD researcher Mark H. Ginsberg, M.D., professor of Medicine at the University of California, San Diego (UCSD) School of Medicine, and his colleagues have identified a mechanism to selectively disrupt signaling to recruit lymphocytes and monocytes – white blood cells sent to sites of inflammation to fight infection – while maintaining the body’s other essential immune system functions. Their findings appear online on February 9 in advance of print publication in the March issue of the Journal of Clinical Investigation.


In the case of certain autoimmune diseases, the alpha 4 integrins cause white blood cells to accumulate at the site of the disease, resulting in inflammation. An integrin is a surface molecule found on the exterior of cells that helps cells adhere and migrate. It is also believed to be responsible for a role in cell signaling, which allows cells to communicate with the extracellular environment. One of the promising treatments for disorders such as multiple sclerosis, inflammatory bowel disease and rheumatoid arthritis – the alpha 4 integrin antagonist – works by blocking cell adhesion. However, this anti-inflammatory therapy could cause adverse side effects, such as impairment of the immune system and the patient’s ability to develop new red and white blood cells in the bone marrow, a process called hematopoiesis.

"Our goal was to identify a more specific target of alpha 4 integrin molecules in order to interfere with their roles in disease progression while sparing alpha4 functions required for normal health," said David M. Rose, D.V.M., Ph.D., assistant professor of medicine at UCSD, and co-author of the study.

The research team created mutant mice known as "alpha4(Y991A) mice," in which the alpha4 integrin can no longer bind to a signaling protein inside the cell called paxillin. Previously generated alpha4 integrin deficient mutant mice died at birth because too many aspects of alpha4 function were changed. The new alpha4(Y991A) mice have an impairment only in the interaction between alpha4 and paxillin, and thus have fewer effects on development. The researchers discovered that, in contrast to normal mice, alpha4(Y991A) mice exposed to an inflammatory stimulus recruited fewer circulating white blood cells (B and T cells) to the region of exposure. However, the development of new B and T cells was unaffected.

The authors suggest that these mice are a valuable tool to test models of inflammatory and autoimmune diseases of humans, and that a new class of pharmaceutical agents that target the specific interaction of paxillin and alpha4 integrin could be important future treatments of inflammatory disease.

"We were surprised to find that the mutation actually had very little effect on the animal’s development of lymphocytes, the white blood cells that fight infection," said Rose. "This could prove to be an important first step in development of a more effective drug to target alpha4 integrins in autoimmune and inflammatory disease of humans."

Additional co-authors include Kenneth Kaushansky, M.D., Chloé C. Féral, Jaewon Han, Norman Fox and Gregg J. Silverman, UCSD Department of Medicine.

Debra Kain | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Health and Medicine:

nachricht Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>