Researchers discover signaling pathway crucial to acute lung injury

Jan 31, 2011

Researchers at National Jewish Health have discovered a signaling pathway that is crucial to the devastating effects of acute lung injury (ALI). The data, obtained from cells, animals and ALI patients, suggest several potential therapeutic targets. Experimental blockade of one of the targets significantly reduced flooding of the lungs that is the hallmark of ALI.

" is a devastating disease, with 40 percent mortality and no beneficial therapies," said first author James Finigan, MD, Assistant Professor of Medicine at National Jewish Health. "Our study identifies several promising targets for therapy, including HER2, which is already targeted by existing breast-cancer medications."

About 200,000 people in the United States suffer acute lung injury (ALI) every year. It is caused by either direct injury to the lungs or as a result of other conditions, often or systemic infection. In ALI, large amounts of protein-rich fluid flow from the capillaries into the lungs, leading to flooding of the airspaces and reduced ability to deliver oxygen to the blood. Severe ALI is often referred to as or ARDS. Currently there is no approved therapy for the disease. Care of ALI patients is supportive only, in which doctors try to maintain blood-oxygen levels. Approximately 40 percent of patients with ALI, or 90,000 people per year in the US, die.

Dr. Finigan and his colleagues had previously shown that HER2, a receptor involved in cell development and growth, participates in recovery of mice from chemically-induced lung injury. They hypothesized that it may also play a role in the earlier inflammatory phase of lung injury, which resembles ALI in mice. The researchers also knew that the inflammatory molecule interleukin-1β is a central player in ALI and the permeability of capillaries.

In a series of experiments in cell culture and animal models they connected interleukin-1β to HER2, which triggers a cascade of signals within epithelial cells. Those signals cause blood vessel walls to become permeable and allow the flood of fluid into the lung airspaces. When researchers blocked production of NRG-1, one of the molecules in the , they reduced flow of molecules through a cellular barrier by 52 percent.

The researches then examined lung fluid from ALI patients, and found heightened levels of NRG-1, adding clinical evidence to their data supporting an important role for this pathway. They published their findings January 19 in the online version of the Journal of Biological Chemistry

Two existing medications, herceptin and tykerb, already target a malfunctioning in some cases of breast-cancer. Several medications targeting ADAM17 are also in development.

"Our work suggests several very promising avenues of research that may finally bring help to ALI patients," said senior author Jeffrey Kern, MD, Professor of Medicine at National Jewish Health.

Explore further: US scientists make embryonic stem cells from adult skin

Provided by National Jewish Health

not rated yet
add to favorites email to friend print save as pdf

Related Stories

Stem cells restore tissue affected by ALI

May 17, 2010

Human stem cells administered intravenously can restore alveolar epithelial tissue to a normal function in a novel ex vivo perfused human lung after E. coli endotoxin-induced acute lung injury (ALI), according to research ...

Recommended for you

Leeches help save woman's ear after pit bull mauling

Apr 18, 2014

(HealthDay)—A pit bull attack in July 2013 left a 19-year-old woman with her left ear ripped from her head, leaving an open wound. After preserving the ear, the surgical team started with a reconnection ...

New pain relief targets discovered

Apr 17, 2014

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

User comments : 0

More news stories

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Study says we're over the hill at 24

(Medical Xpress)—It's a hard pill to swallow, but if you're over 24 years of age you've already reached your peak in terms of your cognitive motor performance, according to a new Simon Fraser University study.

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.