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 The dense vessel network regulates formation of thrombocytes in the bone marrow
25.07.2017 | Rudolf-Virchow-Zentrum für Experimentelle Biomedizin der Universität Würzburg

nachricht Fungi that evolved to eat wood offer new biomass conversion tool
25.07.2017 | University of Massachusetts at Amherst

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

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...

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 mission surfs through waves in space to understand space weather

25.07.2017 | Physics and Astronomy

Strength of tectonic plates may explain shape of the Tibetan Plateau, study finds

25.07.2017 | Earth Sciences

The dense vessel network regulates formation of thrombocytes in the bone marrow

25.07.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>