Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research uncovers signaling pathways related to brain-immune system links

17.05.2006
Cell biology studies may lay groundwork for a novel HIV treatment

New research on signaling pathways in immune cells bolsters evidence of connections between the central nervous system and the immune system. The findings may also advance the scientific foundation for a potential HIV treatment that may block the virus that causes AIDS.

The cell culture study by a research team from The Children’s Hospital of Philadelphia and the University of Pennsylvania appears in the Proceedings of the National Academy of Sciences, published online on May 4.

The team, led by Steven D. Douglas, M.D., chief of the Section of Immunology at The Children’s Hospital of Philadelphia, analyzed neurokinin-1 receptors found on the surfaces of monocytes, immune cells that develop into macrophages. The neurokinin-1 receptors (NK-1R) are docking sites for substance P, a well-known neurotransmitter that plays important roles in both immune function and the nervous system.

In the current study, the Douglas team investigated two forms of NK-1R in a human monocyte/macrophage cell line. One was a full-length receptor, the other a shortened version with fewer amino acids. When the researchers added substance P to cell cultures with the receptors, both responded with an increase in calcium ions, but used distinct signaling pathways.

The truncated NK-IR did not respond directly to substance P, but worked through another signaling molecule, the chemokine RANTES, to increase the calcium flow. The RANTES molecule is important because it binds to another cell receptor, CCR5, which is crucial in allowing common strains of HIV (R5 strains) to infect immune cells.

Significantly, when the investigators added the drug aprepitant, which binds to NK-1R, to their cell cultures, it inhibited signaling from both the full-length and short form of the receptors.

Although the current study was not focused on HIV infection, it directly relates to broader interests of Dr. Douglas’ laboratory. He currently leads a four-year program project grant from the National Institute of Mental Health, entitled, "Neurokinin-1R (Substance P Receptor) Antagonists for HIV Therapy." One project within that grant will conduct a phase 1 (safety) trial of aprepitant in adults with HIV infection. Currently used as an anti-nausea medication, aprepitant, which has the trade name Emend, might also block HIV infection.

Because macrophages are a reservoir for HIV, a strategy that denies the virus entry into those immune cells may be important in combating HIV infection. Dr. Douglas showed in 2001 that another NK-1R antagonist blocked HIV replication within macrophages in cell culture. The hope is that aprepitant may show a similar protective effect in patients.

"We postulate that blocking NK-1R may send signals to turn off the CCR5 receptor for HIV, closing the door to the virus," said Dr. Douglas. "Underlying the signaling mechanisms are the questions, ’how does the immune system talk to the nervous system?’ and ’how does the nervous system talk back?’ Substance P is a link between both systems, and this study increases our understanding of those underlying questions."

John Ascenzi | EurekAlert!
Further information:
http://www.chop.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 >>>