Navigation Links
Scientists discover clues to inflammatory disease

Immune system cells called macrophages spring into action to surround and destroy threats such as viruses or cancer cells. But sometimes the would-be protective response leads to persistent inflammation, which, in turn, can cause disease.

Scientists don't know exactly how macrophages cross the line from being good cops to bad cops, but researchers at the University of Florida recently unearthed several clues about the mechanisms involved. Through the lens of two inflammation-related diseases, HIV and rheumatoid arthritis, they identified changes in specific proteins linked to the action of macrophages, white blood cells that are key to the body's natural defenses.

The findings could lead to new early diagnosis tools and targeted therapy for diseases that stem from abnormal or uncontrolled macrophage activation, including cancer, cardiovascular disease and neurological disorders.

"Macrophage activation is important because it is involved in inflammation, which is involved in a number of diseases," said molecular biologist Maureen Goodenow, Ph.D., the Stephany W. Holloway university chair in AIDS research and professor of pathology, immunology and laboratory medicine in the UF College of Medicine, who led the research. "Chronically inflamed macrophages can be a problem for human health."

The findings, published in April and June in the journals AIDS and Cellular Immunology, built on studies also published in April by the group in the Journal of Leukocyte Biology.

With the advent of powerful antiretroviral therapies, people infected with HIV now survive for decades without progressing to AIDS. Even so, they battle inflammatory conditions such as HIV-associated dementia and cardiovascular disease.

One cause of macrophage activation that researchers are exploring is microbial translocation the spilling of parts of intestinal microbes into the blood circulation. Researchers have proposed that bacterial products thus released can activate immune system T cells and in so doing lead to the progression to AIDS.

One of those pathogen-related proteins spilled into the blood is called LPS. In studies of plasma and blood cells from people infected with HIV, the UF team investigated whether the amount of the protein present was associated with how quickly HIV progressed to AIDS. They found no correlation between the protein levels and depletion of T cells, the hallmark indicator of AIDS. Instead, they found that it was associated with activation of macrophages and their precursor cells, and with inflammation that persisted even after anti-viral therapy.

"This sets the stage to start teasing apart the relative contributions of different causes for immune activation in people with HIV," said Mark Wallet, Ph.D., an immunologist and postdoctoral researcher who is first author of two of the papers. "We can eventually use that information to better treat HIV-infected individuals by targeting the inflammation that causes so many long-term illnesses."

The researchers turned to rheumatoid arthritis to study the role of another molecule called interferon gamma. Produced in inflamed joints, it sets off an immune system process that is completed by a compound found in the natural lubrication fluid of joints. That compound has been shown to inhibit inflammation.

But it might also promote inflammation, the UF team has now shown. They found that in the presence of interferon gamma, the compound acted on macrophages to elevate production of two inflammation-causing proteins and suppress a protein that usually regulates normal immune cell responses.

"We're striving to dissect the initiating events that lead to chronic inflammation," Wallet said. "Immune cell activation and inflammation can become self-sustaining processes that are difficult to silence once a disease has progressed too far."

The researchers learned more about the roles of LPS and interferon gamma through a technique called proteomics, which gives a wealth of information that allows researchers to pinpoint specific changes within cells. It is a major shift from previous methods that rely on measuring secretions or biomarkers produced as a result of unspecified changes in cells.

"It's kind of like molecular archeology. We're getting pieces of a puzzle and trying to reconnect things in a biological context to infer what caused these events and get a better idea of what to focus on for future studies," said Joseph Brown, Ph.D., first author of one of the papers, who now works at Pacific Northwest National Laboratory in Richland, Wash. "What we're trying to do is better understand why the immune system is so off course, so exaggerated."

The work brings to light variations in protein expression patterns that relate to macrophage activation gone awry.

"This type of work is really critical to identifying specific fingerprints target proteins that could be either enhanced or suppressed," said Luis Montaner, D.V.M., M.Sc., D. Phil., editor-in-chief of the Journal of Leukocyte Biology and a professor of immunology at The Wistar Institute, who was not involved in the studies. "Getting a clear definition of what that means in the protein expression site can give the ability to target those proteins rather than the whole sequence."


Contact: Czerne M. Reid
University of Florida

Related biology news :

1. Jefferson scientists deliver toxic genes to effectively kill pancreatic cancer cells
2. Scientists identify novel inhibitor of human microRNA
3. Argonne scientists peer into heart of compound that may detect chemical, biological weapons
4. MU scientists go green with gold, distribute environmentally friendly nanoparticles
5. Scientists identify gene that may contribute to improved rice yield
6. Scientists discover why a mothers high-fat diet contributes to obesity in her children
7. MU scientists see how HIV matures into an infection
8. Earth scientists keep an eye on Texas
9. Thinking it through: Scientists call for policy to guide biofuels industry toward sustainability
10. Scientists identify a molecule that coordinates the movement of cells
11. Scientists Find new migratory patterns for Mediterranean and Western Atlantic bluefin tuna
Post Your Comments:
(Date:4/28/2016)... -- First quarter 2016:   , Revenues ... first quarter of 2015 The gross margin was 49% ... and the operating margin was 40% (-13) Earnings per ... from operations was SEK 249.9 M (21.2) , Outlook ... 7,000-8,500 M. The operating margin for 2016 is estimated ...
(Date:4/15/2016)... CHICAGO , April 15, 2016  A ... companies make more accurate underwriting decisions in a ... offering timely, competitively priced and high-value life insurance ... health screenings. With Force Diagnostics, rapid ... and lifestyle data readings (blood pressure, weight, pulse, ...
(Date:3/31/2016)... 31, 2016   ... the "Company") LegacyXChange is excited to release ... soon to be launched online site for trading 100% ... ) will also provide potential shareholders a sense of ... to an industry that is notorious for fraud. The ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... NY (PRWEB) , ... June 24, 2016 , ... While ... machines such as the Cary 5000 and the 6000i models are higher end machines ... is the height of the spectrophotometer’s light beam from the bottom of the cuvette ...
(Date:6/23/2016)... ... 23, 2016 , ... Mosio, a leader in clinical research ... Recruitment and Retention Tips.” Partnering with experienced clinical research professionals, Mosio revisits the ... tools, and strategies for clinical researchers. , “The landscape of how patients receive ...
(Date:6/23/2016)... 2016   Boston Biomedical , an industry ... to target cancer stemness pathways, announced that its ... Drug Designation from the U.S. Food and Drug ... including gastroesophageal junction (GEJ) cancer. Napabucasin is an ... cancer stemness pathways by targeting STAT3, and is ...
(Date:6/23/2016)... A person commits a crime, and the detective ... the criminal down. An outbreak of foodborne illness ... (FDA) uses DNA evidence to track down the bacteria that ... It,s not. The FDA has increasingly used a complex, cutting-edge ... illnesses. Put as simply as possible, whole genome sequencing is ...
Breaking Biology Technology: