Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

La Jolla Institute scientist discovers key step in immune system-fueled inflammation

02.07.2012
Novel mechanism plays major role in inflammation

Like detectives seeking footprints and other clues on a television "whodunit," science can also benefit from analyzing the tracks of important players in the body's molecular landscape.

Klaus Ley, M.D., a scientist at the La Jolla Institute for Allergy & Immunology, has done just that and illuminated a key step in the journey of inflammation-producing immune cells. The finding provides powerful, previously unknown information about critical biological mechanisms underlying heart disease and many other disorders.

The study, published today in Nature, focuses on one of the body's most abundant and important immune cells, known as neutrophils, which play a pivotal role in many diseases. "Neutrophils are the body's first line of defense and the main cell protecting us from bacterial infections," said Dr. Ley, a pioneer in vascular immunology and head of the La Jolla Institute's Division of Inflammation Biology. "While their protective function is very positive, neutrophils also have inflammation-producing properties that cause problems in heart disease and a host of autoimmune diseases, for example lupus. This makes understanding how to manipulate these cells extremely important in disrupting disease."

National Medal of Science winner Shu Chien, M.D., Ph.D., a UC San Diego professor renowned for his work on vascular mechanisms and atherosclerosis, praised Dr. Ley's finding as a significant advance in understanding inflammatory mechanisms in disease. "They have elucidated the molecular and mechanical bases of this type of neutrophil rolling (in the blood vessels) that have major significance in inflammation," said Dr. Chien, director of UCSD's Institute of Engineering in Medicine. "Since inflammation is at the root of a large variety of diseases, these findings not only have fundamental importance in the mechanobiology of the cell, but also in understanding the pathophysiology of many disease states."

In his Nature paper entitled "'Slings' enable neutrophil rolling at high shear," Dr. Ley revealed how neutrophils use sling-like membrane tethers to latch on to the blood vessel wall during periods when blood flow is very fast. In making the discovery, Dr. Ley and Prithu Sundd, Ph.D., a researcher at La Jolla Institute, used "dynamic footprinting," a pioneering imaging technique they developed in 2010 that uses special microscopes and total internal reflection microscopy to see and photograph the neutrophil adhesion process with unprecedented clarity. Alex Groisman, Ph.D., an associate professor in UCSD's Department of Physics, was instrumental in developing and constructing the microfluidic device in which these experiments were conducted and collaborated on the Nature paper.

Sussan Nourshargh, Ph.D., professor of Microvascular Pharmacology and head of the Center for Microvascular Research at Barts and The London Medical School, University of London, said the work provides another "major insight" from Dr. Ley whose discoveries, over the years, have repeatedly enhanced scientific understanding of the role of neutrophils in causing inflammation. In particular, she cited Dr. Ley's groundbreaking work on the discovery of the leukocyte adhesion cascade, which explained the sequential steps used by neutrophils to clamp onto the blood vessel wall as they prepare to migrate to sites of infection. His latest finding reveals another important step in that process.

"This is a completely new cellular concept that will now be added as an additional step to the leukocyte adhesion cascade that describes the sequential cellular responses involved in guiding neutrophils to sites of inflammation," she said. "This pioneering work will without doubt pave the way for other researchers to explore the occurrence of "slings" in a wide range of inflammatory scenarios."

Like other immune cells, neutrophils travel throughout the body via the blood stream pursuing their infection-fighting duties. In order to accomplish their work, neutrophils must migrate through the blood vessel walls to sites of infection, injury or inflammation.

"The activities of neutrophils are very important for our survival, so they are the subject of significant scientific study," said Dr. Ley. While some scientists study their migration out of the blood vessel, Dr. Ley's lab has focused on how neutrophils adhere to the blood vessel wall. "This is important because it provides an opportunity to develop new treatments based on modulating or blocking one of the steps in the adhesion cascade," said Dr. Ley, noting that earlier studies have shown that blocking even one of the steps can severely reduce neutrophil recruitment.

While Dr. Ley has previously shown how neutrophils adhere when blood flow is slow, his latest study reveals that neutrophils use long membrane tethers at the front of the cell, termed "slings," to slow down during high blood flow. The cells do this by separating their cytoskeleton from the cellular membrane, wrapping the sling around themselves like a lasso and then digging their hooks into the blood vessel wall, said Dr. Ley. High blood flow occurs during inflammation, when the body rushes immune cells to a site to promote healing. Inflammation is a normal part of the healing process, but is unwanted in certain diseases.

"For these cells, adhering under high shear is like being in a huge wind storm," said Dr. Ley. "The challenge in this storm is not to get blown away."

Dr. Ley's studies could prove valuable in helping scientists understand how to reduce adhesion, where inflammation is unwanted, such as in heart or autoimmune disease, or to enhance the process, where more neutrophils are desired, such as in bacterial infections like MRSA. "The body needs to have enough neutrophils to fight off bacteria faster than they can grow," he said. "Better understanding of neutrophil adhesion could be very beneficial in that process. Conversely, interrupting this process could have major impacts in autoimmune and other inflammatory diseases."

About La Jolla Institute

Founded in 1988, the La Jolla Institute for Allergy & Immunology is a biomedical research nonprofit focused on improving human health through increased understanding of the immune system. Its scientists carry out research seeking new knowledge leading to the prevention of disease through vaccines and the treatment and cure of infectious diseases, cancer, inflammatory and autoimmune diseases such as rheumatoid arthritis, type 1 (juvenile) diabetes, Crohn's disease and asthma. La Jolla Institute's research staff includes more than 150 Ph.D.s and M.D.s. To learn more about the Institute's work, visit www.liai.org.

Bonnie Ward | EurekAlert!
Further information:
http://www.liai.org

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 >>>