Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers describe first functioning 'lipidome' of mouse macrophage

02.12.2010
For the first time, scientists have described not only the identities and quantities of fat species in a living mammalian cell – in this case, a mouse macrophage or white blood cell – but they also report how these lipids react and change over time to a bacterial stimulus triggering the cell's immune response.

Writing in the December 17 issue of the Journal of Biological Chemistry, lead author Edward A. Dennis, PhD, distinguished professor of pharmacology, chemistry and biochemistry at the University of California San Diego School of Medicine, said the work culminates more than seven years of effort by scientists in LIPID MAPS, a national consortium of 12 research laboratories at nine "core" universities, medical research institutes and life sciences companies collaborating to study the structure and function of lipids. UC San Diego serves as lead institution and information clearinghouse. Dennis is principal investigator.

"This paper is the essence of what we originally proposed," said Dennis. "This is our big, initial study, though we've published many other papers and have more in the pipeline." All nine core facilities in LIPID MAPS participated in the study.

Until relatively recently, lipid research has not received the same degree of attention as, say, genes or proteins. But fats are indisputably crucial to cell operations and overall health. Lipids represent major structural and metabolic components of cells and perform essential functions, such as membrane construction, energy production and intracellular communications.

"They're also a key in virtually all diseases," said Dennis. "Any condition involving inflammation involves lipids. It's hard to think of a disease, including cancer, in which lipids don't play some role."

Likewise for the subject of the research: the mouse macrophage.

"It would have been simpler to do this with yeast or bacteria," said Dennis, "but the macrophage is found in every kind of mammalian tissue (under different names). It's a major player in the immune system."

Moreover, scientists were able to study natural macrophages obtained from a live, well-established mouse model, rather than relying upon cultured cells. The model could also be genetically modified to test various hypotheses.

Previous studies have produced increasingly expansive and detailed "parts lists" of lipids. In October, for example, Dennis and colleagues published a paper that identified and quantified almost 600 distinct fat species circulating in human blood.

The new paper goes further. It chronicles the activity of more than 400 fat species in a macrophage after exposure to an endotoxin – a molecule found on the surfaces of bacteria that is recognized by macrophages and which triggers the cell's infection-fighting functions.

Each hour for 24 consecutive hours, scientists measured minuscule increases or decreases of targeted lipids, an indication of greater or lesser activity.

"The result is a temporal model of infection at the level of a single cell," said Dennis.

Similar experiments were conducted with macrophages exposed to a statin (a popular class of cholesterol-lowering drugs) and with macrophages simultaneously exposed to both an endotoxin and a statin.

"We chose to use a statin because we know it blocks production of cholesterol (a type of lipid), but statins also produce some anti-inflammatory effects. We wanted to see what else happens. And in fact, we saw some unexpected changes in certain metabolites."

Metabolites are the players and products of metabolism – the set of chemical reactions in cells that produce and sustain life.

Dennis said the findings lay the foundation for on-going and future projects to eventually produce a human "lipidome," a complete inventory of all fat species in the human body and how they work together.

"We only have three more years of the LIPID MAPS project," Dennis said. "But this is really just the beginning."

Co-authors of the paper are Raymond A. Deems of the Department of Chemistry and Biochemistry at UC San Diego; Richard Harkewicz of Department of Pharmacology, UC San Diego School of Medicine; Oswald Quehenberger and Gary Hardiman of UCSD's Department of Medicine, School of Medicine; H. Alex Brown, Stephen B. Milne and David S. Myers of the Department of Pharmacology, Vanderbilt University School of Medicine; Christopher K. Glass of the UCSD's Department of Medicine and Department of Cellular and Molecular Medicine, School of Medicine; Donna Reichart of UCSD's Department of Cellular and Molecular Medicine, School of Medicine; Alfred H. Merrill, Jr., M. Cameron Sullards and Elaine Wang of the Schools of Biology, Chemistry and Biochemistry and the Petit Institute of Bioengineering and Bioscience at Georgia Institute of Technology; Robert C. Murphy of the Department of Pharmacology, University of Colorado Denver; Christian R.H. Raetz, Teresa Garrett, Ziqiang Guan and Andrea C. Ryan of Department of Biochemistry, Duke University Medical Center; David W. Russell, Jeffrey G. McDonald and Bonne M. Thompson of Department of Molecular Genetics, University of Texas Southwestern Medical Center; Walter A. Shaw of Avanti Polar Lipids, Inc; Manish Sud, Yihua Zhao, Shakti Gupta, Mano R. Maurya and Eoin Fahy of the San Diego Supercomputer Center and Shankar Subramaniam of Department of Chemistry and Biochemistry, the Department of Cellular and Molecular Medicine and the San Diego Supercomputer Center, all at UC San Diego.

Funding for this project was provided by the National Institute of General Medical Sciences' Large Scale Collaborative "Glue" grant.

Scott LaFee | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>