Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

U-M scientists target key cells and signals that trigger pulmonary fibrosis

24.05.2006
Research could lead to new treatments, diagnostic tests for IPF

Scientists at the University of Michigan Medical School have identified biochemical signals that attract pathogenic cells to damaged lung tissue – one of the first steps in a chain of events leading to a lethal disease called idiopathic pulmonary fibrosis or IPF.

Idiopathic pulmonary fibrosis is a progressive disease that kills 40,000 Americans each year. Exposure to toxic environmental agents like beryllium and silica dust can trigger IPF, but in most cases, its cause remains a mystery.

"The disease is devastating to the patients who have it, and to the physicians who have no effective ways to treat it," says Bethany B. Moore, Ph.D., an assistant professor of internal medicine at the U-M Medical School. Working with Galen B. Toews, M.D. – a professor of internal medicine and chief of pulmonary and critical care medicine – and other Medical School researchers, Moore studies the cells and signaling pathways involved in IPF.

"IPF gradually destroys air sacs in the lung and replaces them with scar tissue – making it difficult and eventually impossible for patients to breathe," Moore says. "Most patients aren’t diagnosed until the disease is in an advanced stage, and they often die within two years of diagnosis."

By learning more about the basic mechanisms of the disease, U-M scientists hope to uncover new information that could lead to therapeutic drugs to block progressive lung damage or diagnostic tests to make early detection possible.

Moore will present the latest results from her IPF research in a May 23 poster presentation at the American Thoracic Society meeting taking place May 19-24 in San Diego.

Moore studies fibrocytes – primitive cells derived from bone marrow that help repair and restore damaged tissue in the body. When lung tissue is injured, damaged cells send out biochemical distress signals that draw fibrocytes from the bloodstream to the injured area. Once in the lung, fibrocytes turn into fibroblasts – cells that secrete collagen, growth factors and other substances to form scar tissue and help heal the damaged lung. Once repairs are complete, chemical signaling molecules called prostaglandins shut down the influx of fibrocytes and turn off the fibrotic response.

"In pulmonary fibrosis, for reasons we don’t understand, this fibrotic or scar-forming process never shuts down," Moore explains. "Collagen and scar tissue build up in the interstitial spaces between lung cells, making lung tissue sticky and difficult to expand when you inhale. As the disease progresses, people with IPF slowly suffocate to death." In her ATS presentation, Moore will present new evidence indicating that lipid mediators called cysteinyl leukotrienes may be responsible for the inappropriate activation of fibrocytes in fibrotic lungs, while prostaglandins can inhibit fibrocyte function.

"These findings suggest that therapies to block leukotrienes or to enhance prostaglandins may be beneficial to patients suffering from IPF," Moore explains.

In earlier research, Moore discovered that a receptor molecule called CCR2 must be present on the fibrocyte’s surface, in order for fibrosis to begin. Laboratory mice without the CCR2 molecule were unable to attract fibrocytes and did not develop pulmonary fibrosis after lung injury.

When Moore transferred fibrocytes containing the CCR2 receptor into healthy mice, the mice developed more severe fibrosis after lung injuries than mice that did not receive the fibrocyte transplant.

Moore also found that a specific ligand, or chemical signal, called CCL12 in mice, is produced by epithelial cells in damaged lung tissue. Moore’s research indicates that CCL12’s signal recruits fibrocytes from the bloodstream to the area of tissue damage, and helps trigger the fibrotic process.

After Moore’s research indicated the critical role played by fibrocytes in the development of IPF, U-M clinicians began screening blood samples from U-M patients with the disease. According to Moore, they found fibrocytes from IPF patients produced three times the normal amount of collagen.

"Fibrocytes have at least six different receptor molecules on their surface, so there are certainly multiple signaling pathways involved in the development of IPF," Moore says. "But now we know that preventing the binding between the CCL12 ligand and the CCR2 receptor in mice can limit the disease’s development."

The CCL12 ligand in mice is virtually identical to the CCL2 ligand in humans, which is known to be involved in other human lung diseases, according to Moore. So antibodies or small molecules capable of blocking CCL2’s signal could be promising candidates for new drug discovery.

"We may not be able to stop the initial disease process, but perhaps we could keep it from progressing so rapidly," Moore added. "It’s a first step, but an important one, in solving the mystery of this disease. Right now, continued research is the only hope we can offer IPF patients."

Sally Pobojewski | EurekAlert!
Further information:
http://www.umich.edu

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

Ultrathin device harvests electricity from human motion

24.07.2017 | Power and Electrical Engineering

Scientists announce the quest for high-index materials

24.07.2017 | Materials Sciences

ADIR Project: Lasers Recover Valuable Materials

24.07.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>