Research sheds light on how immune system's 'first responders' target infection
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.
Journal reference: Journal of Leukocyte Biology
Provided by University of Texas Medical Branch at Galveston
- Surprising role for suppressive cytokine in antiviral immune responses Sep 15, 2011 | not rated yet | 0
- Researchers find potential new way to fight sepsis Jun 10, 2011 | not rated yet | 0
- Il-22 gene delivers the goods and decreases intestinal inflammation Jan 02, 2008 | not rated yet | 0
- Transcription factor regulates protein that dampens immune responses Jun 17, 2011 | not rated yet | 0
- Researcher identifies new target to prevent fatal flu lung complication Sep 29, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
The Durability of Bone: Long Falls
4 hours ago I am doing a paper on the physics in Valve's Portal and got interested in the "Long Fall Boots" that prevent any damage no matter how far you fall. I...
Is energy convertible to matter?
6 hours ago Can we convert energy to matter?
Rotating electron as a dipole is this right?
8 hours ago An electron as shown by the Stern Gerlach experiment behaves like a dipole (albeit only in one of two states). I have been trying to figure out how...
Dipole term in multipole expansion
12 hours ago Hi. I'm having some difficult in understanding something about the dipole term in a multipole expansion. Griffiths writes the expansion as a sum of...
Bubbles in a Pre-Boiling/Boiling pot of water
13 hours ago How is it that bubbles form on the bottom of a surface of a pot of boiling water? I think that there is probably an elementary answer to this...
Assumptions of Griffith's fracture theory
May 21, 2013 Any experts on Griffith's fracture theory? I am studying the subject and I am having hard time finding out if the theory is valid for all possible...
- More from Physics Forums - Classical Physics
More news stories
(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.
Immunology May 20, 2013 | 4.8 / 5 (22) | 8 |
(Medical Xpress)—Scientists at King's College London have discovered that Vitamin D has the potential to significantly reduce the symptoms of asthma. The study, led by Professor Catherine Hawrylowicz from ...
Immunology May 20, 2013 | 5 / 5 (1) | 0 |
Melbourne researchers have identified an immune protein that has the potential to stop or reverse the development of type 1 diabetes in its early stages, before insulin-producing cells have been destroyed.
Immunology May 20, 2013 | 5 / 5 (5) | 0 |
Raising hopes for cell-based therapies, UC San Francisco researchers have created the first functioning human thymus tissue from embryonic stem cells in the laboratory. The researchers showed that, in mice, ...
Immunology May 16, 2013 | 4.8 / 5 (5) | 0 |
Researchers from CNRS, Université Toulouse III - Paul Sabatier and IRD have elucidated new molecular mechanisms involved in resistance to visceral leishmaniasis, a serious parasitic infection. They have shown that dectin-1 ...
Immunology May 16, 2013 | not rated yet | 0
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
15 hours ago | 4.2 / 5 (5) | 0 |
(Medical Xpress)—Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer's Disease (AD). Now, A. ...
13 hours ago | 4.9 / 5 (11) | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
15 hours ago | 4.6 / 5 (7) | 0 |
An experimental sleeping pill from US drug company Merck is effective at helping people fall and stay asleep, according to reviewers at the US Food and Drug Administration, which could soon approve the new drug.
8 hours ago | 3 / 5 (2) | 0
Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May ...
9 hours ago | 5 / 5 (4) | 0 |
A drug commonly used to treat depression and anxiety may improve a stress-related heart condition in people with stable coronary heart disease, according to researchers at Duke Medicine.
10 hours ago | 5 / 5 (1) | 0 |