Featured Research

from universities, journals, and other organizations

How immune system's 'first responders' target infection

Date:
February 27, 2012
Source:
University of Texas Medical Branch at Galveston
Summary:
Researchers have discovered previously unsuspected aspects of the chemokine guidance system used by the body's first line of defense against 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.

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


Story Source:

The above story is based on materials provided by University of Texas Medical Branch at Galveston. Note: Materials may be edited for content and length.


Journal Reference:

  1. P. Gangavarapu, L. Rajagopalan, D. Kolli, A. Guerrero-Plata, R. P. Garofalo, K. Rajarathnam. The monomer-dimer equilibrium and glycosaminoglycan interactions of chemokine CXCL8 regulate tissue-specific neutrophil recruitment. Journal of Leukocyte Biology, 2011; 91 (2): 259 DOI: 10.1189/jlb.0511239

Cite This Page:

University of Texas Medical Branch at Galveston. "How immune system's 'first responders' target infection." ScienceDaily. ScienceDaily, 27 February 2012. <www.sciencedaily.com/releases/2012/02/120227162803.htm>.
University of Texas Medical Branch at Galveston. (2012, February 27). How immune system's 'first responders' target infection. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2012/02/120227162803.htm
University of Texas Medical Branch at Galveston. "How immune system's 'first responders' target infection." ScienceDaily. www.sciencedaily.com/releases/2012/02/120227162803.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
Too Few Teens Receiving HPV Vaccination, CDC Says

Too Few Teens Receiving HPV Vaccination, CDC Says

Newsy (July 24, 2014) The Centers for Disease Control and Prevention is blaming doctors for the low number of children being vaccinated for HPV. Video provided by Newsy
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile: iPhone Android Web
          Follow: Facebook Twitter Google+
          Subscribe: RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins