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 New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience

nachricht Wintering ducks connect isolated wetlands by dispersing plant seeds
22.02.2017 | Utrecht University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Positrons as a new tool for lithium ion battery research: Holes in the electrode

22.02.2017 | Power and Electrical Engineering

New insights into the information processing of motor neurons

22.02.2017 | Life Sciences

Healthy Hiking in Smart Socks

22.02.2017 | Innovative Products

VideoLinks
B2B-VideoLinks
More VideoLinks >>>