Sugar element of keratan sulfate halts the progress of emphysema

December 27, 2016
Sugar element of keratan sulfate halts the progress of emphysema
Decrease in keratan sulfate by cigarette smoking. Credit: RIKEN

Using a mouse model, scientists from the RIKEN-Max Planck Joint Research Center for Systems Chemical Biology and a number of other institutes have identified a sugar molecule that reduced the inflammatory response and progress of emphysema, a common component of chronic obstructive pulmonary disease (COPD). According to Naoyuki Taniguchi, the leader of the group, this discovery could lead to the development of drugs based on glycans—biological sugar molecules—for the treatment of diseases such as COPD, which is the fourth leading cause of death worldwide.

As part of the research group's work to explore the roles of sugar molecules in health and disease, they found that keratan sulfate, a large negatively charged saccharide found in the small airway of the lung, is decreased in mice that have been exposed to cigarette smoke. They wondered if this decrease might be associated with the damage that smoking causes to the lung. Taniguchi says, "We are not absolutely sure of the mechanism through which smoking leads to a reduction in keratan sulfate, but felt that clearly the reduction is important in thinking about glycan-based strategies for combating emphysema and COPD."

They wondered whether the keratan sulfate might be playing a protective role in COPD. To test the hypothesis, they prepared a repeating disaccharide element of keratan sulfate, named L4, and administered it into two mouse models of emphysema—one a model of emphysema triggered by the enzyme elastase, and the other an exacerbation of smoking-induced emphysema triggered by LPS, a toxin found in bacterial cell walls.

Attenuation by L4 treatment of elastase-induced alveolar damage. Figure shows images of alveoli (left) and CT analysis of extent of emphysema (right). Credit: RIKEN

In the first model, they found that that treatment with L4 prevented destruction of the alveoli—the small air sacs in lungs that are used to exchange gases, and in addition that it reduced the infiltration of a type of white blood cell called neutrophils, which is symptomatic of an , as well as levels of inflammatory cytokines and tissue-degrading enzymes. Although L4 was shown to inhibit these enzymes, they did not find any ability of L4 to directly reduce the production of cytokines or reactive oxygen species, so concluded that the action was also being done indirectly, through mechanisms involving the neutrophils.

In the exacerbation model, they found that the L4 administration prevented the influx of neutrophils. According to Taniguchi, "We found that L4 was as effective as dexamethasone in reducing neutrophil infiltration. This is very exciting, because dexamethasone, the treatment currently used for COPD, is a steroid medication that can have serious side effects and can in some cases make the outcome worse. It will be exciting if we can show that L4—a which we found had no adverse effects in the mice even at high doses—can be used as a treatment for this condition, which exerts a tremendous health burden."

According to Taniguchi, there is still work to be done in the area. "We plan now to try to determine exactly how L4 blocks neutrophil migration, by finding a target receptor protein, and how L4 can suppress inflammation in vivo, as this could give us important insights into the mechanism of COPD progression and how it can be halted."

The work was published in the American Journal of Physiology, Lung Cellular and Molecular Physiology.

Anti-inflammatory effect of L4 in LPS-induced COPD exacerbation model mice. Credit: RIKEN

Explore further: Visualizing how infection exacerbates lung disease

More information: Congxiao Gao et al. A keratan sulfate disaccharide prevents inflammation and the progression of emphysema in murine models, American Journal of Physiology - Lung Cellular and Molecular Physiology (2016). DOI: 10.1152/ajplung.00151.2016

Related Stories

Visualizing how infection exacerbates lung disease

August 23, 2013
Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. The disease, characterized by constricted airways due to bronchitis and emphysema, is commonly seen in smokers but can also be brought on ...

Vitamin A receptor may help protect lungs from smoking, viral infections

May 8, 2015
It's no surprise that smoking is bad for the lungs. But only 10%-20% of long-term smokers will develop serious conditions that affect breathing, such as emphysema and chronic obstructive pulmonary disease (COPD). To understand ...

Reversing smoke-induced damage and disease in the lung

October 13, 2011
By studying mice exposed to tobacco smoke for a period of months, researchers have new insight into how emphysema and chronic obstructive pulmonary disease (COPD) develops. In the October 14th issue of Cell they also report ...

Study reveals COPD linked to increased bacterial invasion

April 27, 2016
Chronic obstructive pulmonary disease (COPD) is a common smoking-related lung illness and the third leading cause of death in the United States. Scientists have long believed that inhaling toxic gases and particles from tobacco ...

Japanese researchers identify a protein linked to the exacerbation of COPD

March 21, 2013
Researchers from the RIKEN Advanced Science Institute and Nippon Medical School in Japan have identified a protein likely to be involved in the exacerbation of chronic obstructive pulmonary disease (COPD). This protein, Siglec-14, ...

Recommended for you

Google searches can be used to track dengue in underdeveloped countries

July 20, 2017
An analytical tool that combines Google search data with government-provided clinical data can quickly and accurately track dengue fever in less-developed countries, according to new research published in PLOS Computational ...

MRSA emerged years before methicillin was even discovered

July 19, 2017
Methicillin resistant Staphylococcus aureus (MRSA) emerged long before the introduction of the antibiotic methicillin into clinical practice, according to a study published in the open access journal Genome Biology. It was ...

New test distinguishes Zika from similar viral infections

July 18, 2017
A new test is the best-to-date in differentiating Zika virus infections from infections caused by similar viruses. The antibody-based assay, developed by researchers at UC Berkeley and Humabs BioMed, a private biotechnology ...

'Superbugs' study reveals complex picture of E. coli bloodstream infections

July 18, 2017
The first large-scale genetic study of Escherichia coli (E. coli) cultured from patients with bloodstream infections in England showed that drug resistant 'superbugs' are not always out-competing other strains. Research by ...

Ebola virus can persist in monkeys that survived disease, even after symptoms disappear

July 17, 2017
Ebola virus infection can be detected in rhesus monkeys that survive the disease and no longer show symptoms, according to research published by Army scientists in today's online edition of the journal Nature Microbiology. ...

Mountain gorillas have herpes virus similar to that found in humans

July 13, 2017
Scientists from the University of California, Davis, have detected a herpes virus in wild mountain gorillas that is very similar to the Epstein-Barr virus in humans, according to a study published today in the journal Scientific ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.