Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Hopkins scientists discover how protein trips up germs

18.02.2010
If bad bacteria lurk in your system, chances are they will bump into the immune system’s protective cells whose job is gobbling germs. The catch is that these do-gooders, known as macrophages, ingest and destroy only those infectious invaders that they can securely hook and reel in.

Now, Hopkins scientists have shown that a healthy immune response depends on a protein called TRPV2 (pronounced trip-vee-two) which, they discovered, is the means by which macrophages capitalize on brief and accidental encounters with nasty bugs.

Reporting in Nature Immunology in the January 31 online edition, the team proves that TRPV2 is necessary not only for macrophages to get a good grip on disease-causing bacteria, but also as the first line of defense, rallying the rest of the immune system to dispose of the most slippery and sizable germs.

“Imagine a fisherman who gets a bite, but is not strong enough to reel it in alone, so he sounds an alarm that brings others in to help,” analogizes Michael Caterina, M.D., Ph.D., associate professor of biological chemistry, Johns Hopkins University School of Medicine. “That’s similar to what’s happening here: A macrophage receptor will bind to a giant germ it encounters, but not tightly enough to secure it. So TRPV2 on the macrophage acts as an alarm: It tells the other receptors around the macrophage to consolidate in that one place to enhance the local binding of that bacteria.”

Ten years ago, Caterina was the first to clone TRPV2 along with a related protein, called TRPV1, which was found to be involved in sensing painful heat. His lab first looked at the nervous system in an attempt to ferret out TRPV2’s function, but changed tack when it became apparent that this protein is abundant in the immune system, particularly in macrophages.

To learn what role TRPV2 might play in fighting infection, Tiffany Link, a graduate student in Cellular and Molecular Medicine, harvested macrophages from the bellies of two sets of mice: a “wild type” control group, and a group that had been genetically engineered to lack TRPV2. She grew the normal immune cells and the engineered mutant cells in separate dishes, and then added latex beads that were coated with antibody molecules. The normal immune cells efficiently gobbled the beads, while the mutant cells lacking TRPV2 couldn’t ingest nearly as well, indicating that TRPV2 was important in proper functioning of macrophages.

Because the defective macrophages weren’t completely inept in their germ-eating job, Caterina suspects that other proteins like TRPV2 are likely players, too, but TRPV2 clearly makes the germ-clearing process more efficient.

Link, who investigated each separate step macrophages take to successfully consume bacteria, found that in the mutant cells lacking TRPV2, the problem existed from the very moment of initial contact with a germ.

“Without TRPV2, macrophages don’t bind bacteria and engulf them right away,” Link says, “and as a result, the rest of the immune system doesn’t get involved and clear the infection,” Link says.

In order to find out if a mouse missing TRPV2 would be more susceptible to bacterial infection, Link injected live bacteria into the bellies of wild-type mice and those lacking TRPV2. The mice lacking TRPV2 died within four days of infection — significantly sooner than the wild types which died within eight days after infection.

Citing the fact that TRPV2 is important not only in helping macrophages to bind to germs, but also in clearing bacterial infection, Caterina noted its potential as a useful drug target. And in cases of autoimmune diseases — arthritis, lupus and asthma, for example — it’s possible that the inhibition of TRPV2 might help pull back an overactive immune system.

“We think there are going to be a lot of implications beyond just prevention of infectious diseases where this research about TRPV2’s function in macrophages might be relevant,” Link adds. “Macrophages consume cholesterol and contribute to hardening of the arteries. They also clear out debris when nerves are injured so that new nerves can grow through that area.”

The research was funded by the National Institutes of Health.

In addition to Caterina and Link, authors of the paper are Una Park, Becky M. Vonakis, Daniel M. Raben, Mark J. Soloski, all of Johns Hopkins.

On the Web:
http://neuroscience.jhu.edu/MichaelCaterina.php
http://www.nature.com/ni/index.html
Related Video:
Johns Hopkins scientist Michael Caterina tells about the history of the TRP channel.

http://www.youtube.com/user/JohnsHopkinsMedicine#p/u/0/GGL-QSVUW3s

Johns Hopkins researcher Tiffany Link defines TRPV2 as an ion channel.
http://www.youtube.com/user/JohnsHopkinsMedicine#p/u/0/aR0meSN23lo
Media Contacts:
Maryalice Yakutchik; 443-287-2251; myakutc1@jhmi.edu
Audrey Huang; 410-614-5105; audrey@jhmi.edu

Maryalice Yakutchik | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>