Acute lung injury, a disorder of acute inflammation, is a leading cause of death in critical care in Canada. But in a study published yesterday in Cell, University of Calgary researchers have discovered a novel way to stop harmful inflammation in the lungs.
In Canada, 1 in 18 deaths is connected to sepsis—a condition that occurs when the body is fighting off severe infection. What happens during sepsis is that the immune system goes into overdrive, resulting in the accumulation of white blood cells and severe inflammation. This accumulation causes damage to internal organs, like the lungs, and can lead to death. Additionally, inflammation caused by injury and other diseases can also create this response.
The researchers, wanting to find a signal that would cause white blood cells to collect, targeted the lining of blood vessels in the lungs. What they found was a molecule called dipeptidase-1 that could bind with white blood cells and help them pass from the blood into the tissue. As long as any dipeptidase-1 is present, white blood cells continue to bind them. However, by injecting their newly developed drug into the blood stream, the scientists could prevent this binding from taking place.
“We discovered that, by targeting this molecule, we can stop the ill effects of sepsis, acute lung injury, and death,” says coauthor Paul Kubes. “It could have an impact on any inflammatory condition in which lung injury is a contributor to worsening a patient’s condition.”
With this knowledge, the researchers have found a similar process that occurs in the liver and have patented two drug-like molecules that can prevent lung and liver damage due to inflammation. While all of the research to date has been performed on mice, a phase I clinical trial is underway to begin human testing.
The researchers are also applying the findings to cancer metastasis in hopes that this new understanding could lead to treatments to stop cancer cells from spreading in the body and targeting the liver and lungs.
“The molecule we discovered binds to both white blood cells and certain cancer cells,” says coauthor Donna Senger. “We’ve developed a way to stop the white blood cells from binding and moving into the tissue. Now, we’re hoping to find a solution to prevent cancer cells from spreading to these organs.”