New fluorescent probe technique gives hope for killer lung disease

A team of researchers in Germany has used a new technique to shed light on the development of chronic inflammatory lung diseases such as emphysema and bronchitis. The study, which was partly funded by the EU, is published in the journal Nature Chemical Biology. The scientists, from EMBL (European Molecular Biology Laboratory) and the Molecular Medicine Partnership Unit (MMPU) both at the University of Heidelberg, Germany, used a fluorescent probe that may be adapted in the future for diagnosis of chronic inflammatory lung diseases.

The study was partially funded under the MOLECULAR IMAGING (Integrated technologies for in-vivo molecular imaging) project which has EUR 11 million of EU funding under the "Life sciences, genomics and biotechnology for health" Thematic area of the Sixth Framework Programme (FP6), and the AIRWAY DISEASE (Pathogenesis and treatment of chronic airway disease: novel animal models for studies on modifier genes, lung repair mechanisms and novel therapeutic strategies) project, which is financed under the "Human resources and mobility" (Marie Curie Actions) budget line of FP6.

Chronic inflammatory lung diseases, such as bronchitis and emphysema, are serious global health problems. They are the fourth leading cause of death and disability in developed countries and smoking is responsible for 90% of their development.

The research team used a new technique for testing the activity of MMP12, which is an enzyme that is known to be involved in the development of emphysema. Emphysema causes damage to and destruction of the alveoli, the millions of tiny air sacs in the lungs which are crucial for normal breathing.

The MMP12 enzyme is secreted by macrophages, immune cells that defend the body against invaders. In the lungs, macrophages are called into action when foreign material such as cigarette smoke enters. MMP12 helps the macrophages to break down the network of protein and fibres that surround and support the body's cells. This is an important process for wound healing. But overstimulation of macrophages can lead to a build up of MMP12, which can then begin to damage the structure of the alveoli. This then leads to the development of emphysema.

The research team developed a technique involving a fluorescent probe that allows the activity of MMP12 in the lungs to be measured by the amount of fluorescence it takes up. The team carried out the test in a mouse model of acute lung inflammation and found that inflammation increased the activity of MMP12.

"We developed a tool which for the first time allows us to study MMP12 activity in specific cells, as if we were actually looking inside the lungs," said Dr Carsten Schultz, whose group carried out the research at EMBL.

The team hopes that after further research, the new technique will be adapted for use in patients. "This would allow us to use MMP12 as a biomarker to monitor disease evolution and the risk of emphysema formation," said Dr Marcus Mall, group leader at the Children's Hospital at the University of Heidelberg. "It could also serve to examine the response to therapeutic interventions in patients with inflammation lung diseases."

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