EMBL: new diagnostic test for inflammatory lung diseases

05 Aug 2009 | News

Research lead

Work by scientists at the European Molecular Biology Laboratory (EMBL) and its Molecular Medicine Partnership Unit (MMPU) with the University of Heidelberg, Germany, has shed new light on the underlying disease process of the lung disease emphysema, using a technique which could be adapted for use in diagnosis.

The researchers have devised a new strategy for testing the activity of MMP12, an enzyme involved in the development of emphysema. Emphysema is characterised by the damage and destruction of the alveoli, the air-sacs of the lungs that are crucial for respiration and uptake of oxygen.

The disease process is initiated when cigarette smoke and other irritants activate immune cells such as macrophages to destroy the foreign material in the lungs. Chronic exposure causes inflammation. MMP12 is an enzyme secreted by macrophages which usually helps them to break down the extracellular matrix, a process important for normal wound healing. However, over-stimulation of macrophages by irritants leads to build up of excess MMP12, which starts to damage the delicate structure of the small airspaces of the lungs, eventually leading to emphysema.

“We [have] 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 Carsten Schultz, whose group carried out the research at EMBL.

The researchers have designed a fluorescent probe that makes it possible to quantify MMP12 activity in macrophages. Applying this test to samples of lung cells from a mouse model of acute lung inflammation showed the increase in MMP12 activity in macrophages.

The test could be adapted for use in patients. “It would allow us to use MMP12 as a biomarker to monitor disease evolution and the risk of emphysema formation. It could also serve to examine the response to therapeutic interventions in patients with inflammatory lung diseases,” said Marcus Mall, group leader at the Children's Hospital at Heidelberg University.

The researchers hope that the new testing strategy can be extended to other enzymes involved in lung inflammation.


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