Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New metabolic mechanisms discovered that regulate the macrophage's role in immune response

18.03.2015

A group of researchers from Washington University in St. Louis, Agios Pharmaceuticals and ITMO University has discovered new metabolic mechanisms that regulate macrophage polarization - the unique ability of these immune cells to change their specialization depending on the required task. The research opens new possibilities for the development of a new class of drugs based on controlling the metabolism of immune cells. The results were published today in the Immunity journal.

One of the key properties of macrophages is their ability to assume different states in accordance with the environmental factors. For example, resident macrophages (M0) can undergo classical activation and transform into proinflammatory macrophages (M1) that by all means seek to destroy pathogens.


This is a map of macrophage metabolism.

Credit: Alexey Sergushichev

There exists, however, an alternative activation procedure, wherein macrophages acquire an anti-inflammatory healing function (M2). Understanding these processes is extremely important for understanding the immune system as a whole as well as for fighting autoimmune diseases.

Macrophage polarization is accompanied by changes on both transcriptional and metabolic levels. Activation significantly alters the expression of some genes and the concentration of used and produced compounds. While some aspects of activation are known, until recently, the big picture remained elusive.

To study macrophage polarization, the scientists developed the method of non-targeted analysis of metabolic changes based on data obtained from the simultaneous use of RNA sequencing and high-throughput mass spectrometry of metabolites. The researchers combined the data on the basis of the network of biochemical reactions, which allowed them to identify the most significant of the ongoing reactions.

The final set of reactions revealed unknown metabolic mechanisms associated with macrophage polarization. Based on this information, the scientists determined the most probable metabolic pathways that manifest themselves in classical and alternative activations.

The pathways were confirmed using 13C and 15N isotope labeling and pharmacological inhibition experiments. One of the new mechanisms described in the work is the dependence of alternative macrophage activation on glutamine concentration in the environment, which regulates the activity of TCA cycle, and the synthesis of UDP-Glc-Nac - the compound necessary for post-translational protein modification.

"We developed a method of simultaneous analysis of metabolic and transcriptional data. The method proved to be effective and, most importantly, yielded a concrete biological result. Now we continue to improve the method and apply it to other biological tasks such as studying cancer metabolism," says Alexey Sergushichev, PhD student at Computer Technologies Department of ITMO University.

In the long run, the ability to regulate pro- and anti-inflammatory activity can lead to the creation of a new class of drugs based on controlling the metabolism of immune cells. For the first time, macrophage polarization was described in such detail and on such a scale. The work made it possible not only to reveal new regulatory mechanisms of polarization, but also identify and describe the global restructuration of metabolic pathways during polarization. The researchers hope their work will give new impetus to the investigation of pharmacological potential of polarization regulators, which also represents the next step in the collaborative work of the group.

###

The press office of ITMO University thanks Alexey Sergushichev and Maxim Artyomov for their help in preparing this press release.

Dmitry Malkov | EurekAlert!

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>