APR 24, 2015 9:11 AM PDT

Finding Points to a Cause of Chronic Lung Disease

WRITTEN BY: Ilene Schneider
Scientists have long suspected that respiratory viruses - the sort that cause common colds or bronchitis - play a critical role in the long-term development of chronic lung diseases such as asthma and chronic obstructive pulmonary disease (COPD).
New research explains how immune cells called macrophages in the lung sometimes stick around too long, even after clearing a viral infection, leading to long-term lung problems.
Studying mouse and cell models of this process, researchers at Washington University School of Medicine in St. Louis now have shown how immune cells dispatched to the lung to destroy a respiratory virus can fail to disperse after their job is finished, setting off a chain of inflammatory events that leads to long-term lung problems.

Understanding such details may help scientists find ways to block the accumulation of inflammatory immune cells and prevent progression to chronic lung disorders.

The study appears April 20 in The Journal of Experimental Medicine.

The findings stem from research into immune cells called macrophages.

"In general, scientists thought this type of macrophage was involved in the repair of the lung," said senior author Michael J. Holtzman, MD, the Selma and Herman Seldin Professor of Medicine at the School of Medicine. "That may be true in some cases. But like many things in nature, too much of a good thing can become a bad thing."

When large numbers of this type of macrophage accumulate, they appear to stop orchestrating the immune response against acute viral infections and instead participate in a type of response that is more typically directed against parasites and allergens. Holtzman and his colleagues observed that macrophages producing this type of immune response also express a protein called TREM-2 at high levels.

The new work shows that the usual cell-surface form of TREM-2 is indeed needed to sustain the macrophages as they fight off viral infection and the early illness it causes. Then, after the initial infection is cleared, TREM-2 is cleaved from the outer surface of the macrophages. Previously, this cleaved form of the protein was thought to be inactive.

"We were surprised to find that this cleaved form of TREM-2 is actually quite active," Holtzman said. "It potently prevents the programmed death of macrophages, promoting their survival. So this form of TREM-2 allows for macrophages to hang around longer than they should."

Holtzman noted that TREM-2 enables a feed-forward process for inflammatory disease. Each new infection activates macrophages, which later produce the cleaved form of TREM-2. This form then promotes further macrophage accumulation and ultimately contributes to ongoing and progressive inflammatory disease.

Implicating TREM-2 in the harmful accumulation of inflammatory immune cells opens the door to exploring ways to block it, according to first author Kangyun Wu, PhD, a staff scientist.

"We don't yet have a specific drug to interrupt the TREM-2 process," Holtzman said. "But we now understand the controls for the process, so our drug discovery program is already screening for compounds that might keep TREM-2 at normal levels."

The researchers also found that the cleaved form of TREM-2 that causes the macrophages to stick around when they shouldn't does not appear to be involved in the initial immune response to the acute viral infection. So presumably, blocking it should not interfere with the important task of clearing the respiratory virus from the lungs.

Holtzman also pointed out that individual genetic variation in TREM-2 may explain why some people never develop chronic lung disease even after many viral lung infections.

While this study focused on the lung, Holtzman said TREM-2 could be involved in other inflammatory diseases in which the immune system is chronically activated in other organs. He pointed to a possible role in the brain, for example, since related work has associated certain genetic variants of TREM-2 and macrophage dysfunction with Alzheimer's disease.

Source: Washington University in St. Louis
About the Author
  • Ilene Schneider is the owner of Schneider the Writer, a firm that provides communications for health care, high technology and service enterprises. Her specialties include public relations, media relations, advertising, journalistic writing, editing, grant writing and corporate creativity consulting services. Prior to starting her own business in 1985, Ilene was editor of the Cleveland edition of TV Guide, associate editor of School Product News (Penton Publishing) and senior public relations representative at Beckman Instruments, Inc. She was profiled in a book, How to Open and Operate a Home-Based Writing Business and listed in Who's Who of American Women, Who's Who in Advertising and Who's Who in Media and Communications. She was the recipient of the Women in Communications, Inc. Clarion Award in advertising. A graduate of the University of Pennsylvania, Ilene and her family have lived in Irvine, California, since 1978.
You May Also Like
APR 21, 2020
Clinical & Molecular DX
APR 21, 2020
Skin Deep: Handheld Device Sees the Earliest Signs of Cancer
Researchers have developed a handheld device that can image structures under the skin at resolutions 100 times greater t ...
APR 25, 2020
Cannabis Sciences
APR 25, 2020
Researchers Trial Cannabis to Treat COVID-19
Researchers in Israel are investigating the potential for cannabis-derived products to treat patients with COVID-19. So ...
APR 26, 2020
Cannabis Sciences
APR 26, 2020
History of Cannabis Dependence Goes Hand in Hand with Poor Mental Health
As legal restrictions loosen around the recreational use of cannabis, researchers are becoming increasingly concerned ab ...
APR 27, 2020
Microbiology
APR 27, 2020
CDC Adds to the List of COVID-19 Symptoms
The pandemic virus that causes COVID-19 has now infected nearly 3 million people, and killed over 200,000.
MAY 09, 2020
Chemistry & Physics
MAY 09, 2020
Blood test monitors fat intake
Research published in the Journal of Lipid Research highlights a new blood test that is able to monitor an individual&rs ...
MAY 24, 2020
Chemistry & Physics
MAY 24, 2020
The debate on using oilfield produced water for crop irrigation continues
In an attempt to determine whether it is safe to use oilfield produced water for crop irrigation, a team of researchers ...
Loading Comments...