Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Probing the surface of white blood cells to enhance immune system medicine

31.08.2004


White blood cells are the principle mediators of immune system function, yet efforts to influence their role in illness have been hampered due to a lack of understanding of the surface structure of these cells - until now. Dartmouth Medical School researchers characterize the structure of white blood cells and challenge assumptions about how a certain immunodeficiency disorder affects the white blood cell surface in the September 1 issue of Blood, the journal of the American Society of Hematology. Their findings could have a large impact on treatments for autoimmune diseases such as diabetes, rheumatoid arthritis and lupus, as well as AIDS and cancer metastasis.



The researchers, led by Henry N. Higgs, assistant professor of biochemistry at Dartmouth Medical School used scanning electron microscopy to analyze the finger-like projections coating white blood cells known as microvilli. "If you asked most medical scientists what a white blood cell looked like they would say a smooth sphere that floats around in the blood, but, in fact, they are not smooth at all - they have these wonderful invaginations and protrusions coming off of them," explained Higgs, who is also a member of the Immunology and Cancer Immunotherapy Research Program at Norris Cotton Cancer Center and a member of the program in immunology.

Higgs and his lab focused much of their work on lymphocytes a type of white blood cell that have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and disease. An essential feature of lymphocytes’ ability to mount an immune response is their ability to migrate from the blood into infected tissues. The process of squeezing between the cells lining blood vessel walls and into the surrounding tissue is known as ’extravasation.’ Research indicates that microvilli may play a key role in this process. They allow white blood cells hurtling through the bloodstream at speeds analogous to a car traveling at 500 miles per hour to attach to the vessel wall and roll to a stop.


Disruption of the putative receptors on microvilli tips that mediate this process could have significant therapeutic benefits. Drugs that eliminate lymphocyte microvilli could lead to a less toxic form of immune suppression for transplant recipients. Since many cancer cells share the same mechanism of extravasation as lymphocytes, ablating microvilli could also prevent metastasis of cancer cells to distant parts of the body. Similarly, by thwarting lymphocyte migration to deposits of cholesterol in coronary arteries, drugs could prevent the atherosclerosis that leads to heart attacks.

Higgs extended this work to compare lymphocytes in patients with Wiskott-Aldrich syndrome, a hereditary immune disorder that affects males and manifests itself through low platelets and recurrent bacterial infections. These conditions can eventually cause a fatal hemorrhage or infection in these patients. Higgs and his team found no differences in the length or density of microvilli on the lymphocytes, despite expressing little to no Wiskott-Aldrich syndrome protein (WASP)Ñthe protein whose deficiency leads to the syndrome. This challenges the long-held view that an absence of WASP led to the inability to form microvilli on lymphocytes.

The study represents the first quantitative characterization of lymphocyte microvilli and, in addition to characterizing their length and density, the research indicates that microvilli are dynamic structures that rapidly alternate between states of assembly and disassembly. This means that if researchers were able to biochemically dissect mechanisms by which microvilli assemble and segregate, they would be able to use this knowledge to develop immunosuppressive or anti-metastatic agents, enhancing the treatment of cancer and other diseases. Higgs and other Dartmouth medical researchers are working to investigate this promising tool through funding from a $12 million Centers of Biomedical Research and Excellence (COBRE) grant awarded by the NIH in 2003.

The researchers will continue their work in hopes of determining the proteins that assemble lymphocyte microvilli. Identification of these proteins would provide a specific target for drug therapy. "If there is one key protein involved in this process then there is the potential to basically figure out what chemical you could jam into a site on this protein -- sort of like wedging a door open so it doesn’t shut," explained Higgs. "And we want to make sure that wedge doesn’t prop any other doors open that should stay closed."

Other institutions that took part in this research are the University of Toronto and Ludwig-Maximilians University in Munich, Germany. The research was supported by the American Cancer Society, the National Institutes of Health, the Pew Biomedical Scholars and the Canadian Institutes of Health Research.

Andrew Nordhoff | EurekAlert!
Further information:
http://www.dartmouth.edu

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>