Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Disabling infection-fighting immune response speeds up wound healing in diabetes

19.06.2015

One of the body's tools for fighting off infection in a wound may actually slow down the healing process, according to new research by a team of Harvard University, Boston Children's Hospital, and Penn State University scientists. In a study published online in Nature Medicine on June 15, 2015, the researchers show that they can speed up wound healing in diabetic mice by preventing immune cells called neutrophils from producing structures called NETs (neutrophil extracellular traps) that trap and kill bacteria.

"In the fight against bacterial infection, NETs cause collateral damage that slows healing," said Yanming Wang, associate professor of biochemistry and molecular biology at Penn State and a member of the research team.


One of the body's tools for fighting off infection in a wound may actually slow down the healing process, according to new research published online in Nature Medicine on June 15, 2015, by a team that includes scientists at Penn State University, Harvard University, and Boston Children's Hospital. The researchers have speeded up wound healing in diabetic mice by preventing immune cells called neutrophils from producing structures called NETs (neutrophil extracellular traps) that trap and kill bacteria. In this image the structure colored in blue is chromatin -- the condensed form of DNA that the cell remodels to form chromosomes. The enzyme PAD4 decondenses chromatin by loosening up the interaction between DNA and special proteins called histones. The histones modified by PAD4 are shown in fuchsia. This process helps to form both a bacteria-killing NET -- which is comprised of infection-combatting white blood cells called neutrophils -- and the fluffy, scattered ball that comprises a blood clot.

Credit: Wang lab, Penn State University. (Image originally was published in the Journal of Cell Biology).

NETs are thought to reduce the risk of infection in a wound but they also form a dense, toxic mesh that interferes with the mobilization of new healthy cells and hinders tissue repair. The process is even more of a problem in individuals with diabetes, whose neutrophils produce more NETs. As a result, delayed wound healing is a common complication of both type 1 and type 2 diabetes.

To see how diabetes increases a neutrophil's ability to produce NETs, the researchers examined neutrophil cells from patients with either type 1 or type 2 diabetes. They found that these neutrophil cells contained four times the normal amount of the PAD4 enzyme -- a protein that catalyzes the production of NETs. Further experiments revealed that neutrophils from healthy donors or mice that were exposed to excessive glucose -- mimicking diabetes -- also were more likely to release NETs than neutrophils that were exposed to normal glucose levels.

Diabetic mice in the study had more NETs in wounds and healed more slowly than normal mice. However, when the team examined diabetic mice that lacked the PAD4 enzyme they found that the wounds of these mice healed more quickly. "Neutrophils of individuals with diabetes are primed to form NETs by high levels of PAD4, but when we eliminate or control the expression of the PAD4 enzyme in mice with diabetes, we can prevent NETs from forming and speed up healing," Wang said. "It remains to be tested if pharmacological intervention of PAD4 activity will benefit the healing process."

"NETs predispose patients to inflammation, heart disease, and deep-vein thrombosis -- dangerous blood clots that form within veins deep inside the body -- all of which are elevated in patients with diabetes," said the senior author of the study Denisa Wagner, senior investigator of the Program in Cellular and Molecular Medicine at Boston Children's Hospital and Edwin Cohn Professor of Pediatrics at Harvard Medical School. "Any injury that causes inflammation will result in the production of NETs, and we think that if the injury involves skin repair, NETs will hinder the repair process."

When the skin is cut or broken, the body mobilizes a complicated array of cells and proteins to stop bleeding, prevent infection by triggering inflammation, and start the healing process. As part of the inflammatory response, neutrophils, which ingest and destroy bacteria, expel their own chromatin -- a mix of DNA and associated proteins -- in the form of NETs within the wound.

To see whether breaking up the NETs would have an effect similar to preventing their production, the research team treated mice with DNase 1 -- an enzyme that breaks up DNA and therefore can destroy NETs. After three days, wounds on DNase 1-treated diabetic animals were 20 percent smaller than on untreated animals. Interestingly, DNase 1 treatment appeared to accelerate wound healing in healthy mice, as well.

"The anti-microbial function of NETs may have been more important in the days before antibiotics were common and infections were a more pressing concern for human health," said Wang. "Now, as humans live longer lives, we may be able to reduce the detrimental effects of NETs in chronic diseases like diabetes, rheumatoid arthritis, and heart disease by controlling expression of the PAD4 enzyme."

###

In addition to Wang and Wagner, other members of the research team are Siu Ling Wong, Melanie Demers, and Kimberly Martinod from Boston Children's Hospital and Harvard Medical School; Maureen Gallant from Boston Children's Hospital; and Allison B. Goldfine and C. Ronald Kahn from the Joslin Diabetes Center at Harvard Medical School.

The study was supported by the American Diabetes Association (Innovation Award 7-13-IN-44); three institutes of the National Institutes of Health: the National Heart Lung and Blood Institute (grant number R01HL102101), the National Cancer Institute (grant number R01HL136856), and the National Institute of Diabetes and Digestive and Kidney Diseases (grant number R01DK031036); and a GlaxoSmithKline/Immune Disease Institute Alliance Fellowship.

CONTACTS

Yanming Wang: yuw12@psu.edu@psu.edu, 814-441-7404

Barbara Kennedy (PIO): science@psu.edu, 814-863-4682

www.psu.edu

Barbara Kennedy | EurekAlert!

Further reports about: DNase Diabetes PAD4 enzyme immune immune response neutrophils wound healing

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>