Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research sheds light on how immune system's 'first responders' target infection

28.02.2012
University of Texas Medical Branch at Galveston researchers have discovered previously unsuspected aspects of the guidance system used by the body's first line of defense against infection.

The new work focuses on the regulation of immune response by two forms of the signaling molecule IL-8, as well as IL-8's interaction with cell-surface molecules called glycosaminoglycans (or GAGs for short).

Infected or injured tissues release IL-8 to attract bacteria- and virus-killing white blood cells known as neutrophils, a process known as "recruitment." As IL-8 proteins disperse from the infection site, they anchor themselves to GAGs to provide "signposts" that help neutrophils find their target.

"Neutrophils are killing machines but they're also blind, so they shoot at anything and everything — to fight infection effectively and minimize collateral tissue damage, they have to be precisely directed and activated," said UTMB associate professor Krishna Rajarathnam, lead author of a paper on the study in the Journal of Leukocyte Biology. "This process of spatial and temporal control is quite complex, but we've gained a fundamental insight into a very basic mechanism."

That mechanism is based on IL-8's existence as both a single unit (a monomer) and a pair (a dimer). In nature, during the course of onset and resolution of infection, IL-8 could exist as a monomer, dimer, or both.

To study how this process affects immune response, Rajarathnam and his colleagues created two forms of IL-8 not found in nature: one made of monomers unable to join into dimers, and the other of dimers unable to split into monomers. They then carried out a series of mouse experiments with monomers, dimers and "wild-type" (normal) IL-8 in which they found that differing concentrations of IL-8 monomer and dimer clearly influenced the strength of neutrophil recruitment.

In addition, drawing on earlier work, they determined that these effects varied depending on the location of the infection — leading them to the conclusion that IL-8 monomers and dimers interact differently with GAGs in different body tissues.

"Our previous experiments involved IL-8 in the lung, and in this study we looked at what happened if we injected IL-8 in the peritoneum, the abdominal wall," Rajarathnam said. "In the lung, the neutrophil activity we saw for wild-type IL-8 was between the monomer alone or the dimer alone, but in the peritoneum the wild type actually produced greater activity. It was synergistic, meaning that in the wild type the monomer and the dimer interact cooperatively to facilitate neutrophil recruitment."

Such unpredictable results are to be expected when investigating a phenomenon as complex as immune response, according to Rajarathnam.

"I believe we have discovered a crucial and fundamental mechanism that regulates neutrophil function," Rajarathnam said. "Our future goal is to characterize the distinct activities of monomer and dimer to see if we can 'control' runaway inflammation and related neutrophil-induced tissue damage in diseases such as sepsis."

Other authors of the paper include graduate student Pavani Gangavarapu, assistant professor Lavanaya Rajagopalan, instructor Deepthi Kolli, assistant professor Antonieta Guerrero-Plata and Dr. Roberto Garofalo.

"This was a truly translational project, bringing together researchers from both basic and clinical sciences to study the molecular mechanisms underlying disease," Rajarathnam said.

This work was supported by a grant from the National Institutes of Health.

Jim Kelly | EurekAlert!
Further information:
http://www.utmb.edu

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

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

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>