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 | Source: EurekAlert!
Further information: www.chop.edu
More articles from Life Sciences:
New genetic research finds shark, human proteins stunningly similar
06.12.2013 | Cornell University
Prostate cancer biomarker may predict patient outcomes
06.12.2013 | Vanderbilt University Medical Center
International team of scientists develops new feedback method for optimizing the laser pulse shapes used in the control of chemical reactions
In many ways, traditional chemical synthesis is similar to cooking. To alter the final product, you can change the ingredients or their ratio, change the method of mixing ingredients, or change the temperature or pressure of the environment of the ingredients.
Like an accomplished chef, chemists have become very skilled ...
A genetic defect protects mice from infection with influenza viruses
A new study published in the scientific journal PLOS Pathogens points out that mice lacking a protein called Tmprss2 are no longer affected by certain flu viruses.
The discovery was made by researchers from the Helmholtz Centre for Infection Research (HZI) in Braunschweig in collaboration with colleagues from Göttingen and ...
The Light: Global study gets underway with online user survey
Light has a fundamental impact on our sense of well-being and performance. In cooperation with Zumtobel, a supplier of lighting solutions, Fraunhofer IAO has launched a global user survey of lighting quality in offices. The objective is to identify the best lighting conditions for a variety of spaces and lighting ...
Quantum entanglement, a perplexing phenomenon of quantum mechanics that Albert Einstein once referred to as “spooky action at a distance,” could be even spookier than Einstein perceived.
Physicists at the University of Washington and Stony Brook University in New York believe the phenomenon might be intrinsically linked with wormholes, hypothetical features of space-time that in popular science fiction can provide a much-faster-than-light shortcut from one part of the universe to another.
But here’s the catch: One couldn’t actually ...
A star is formed when a large cloud of gas and dust condenses and eventually becomes so dense that it collapses into a ball of gas, where the pressure heats the matter, creating a glowing gas ball – a star is born.
New research from the Niels Bohr Institute, among others, shows that a young, newly formed star in the Milky Way had such an explosive growth, that it was initially about 100 times brighter than it is now. The results are published in the scientific journal, Astrophysical Journal Letters.
The young ...
06.12.2013 | Materials Sciences
06.12.2013 | Life Sciences
06.12.2013 | Life Sciences
05.12.2013 | Event News
04.12.2013 | Event News
12.11.2013 | Event News