Researchers find a way to stop lung damage due to sepsis and injury

Researchers have discovered a way to stop harmful inflammation in the lungs due to sepsis and injury.

They found a molecule present during inflammation that binds to white blood cells allowing them to pass from the bloodstream into the tissue and cause severe damage.

"This work demonstrates the power of collaboration in solving complex health issues to benefit patients. The research involved teams from 10 laboratories, nine at UCalgary with investigators from the Arnie Charbonneau Cancer Institute and the Snyder Institute for Chronic Diseases," said Robbins, a professor in the department of Oncology, and Biochemistry & Molecular Biology and Scientific Director of the CIHR Institute of Cancer Research.

Sepsis occurs when the body is fighting off a severe infection. The immune system goes into overdrive sending white blood cells to clear up the infection. The battle between your immune system and the infection leads to inflammation.

In some cases instead of cleaning up and moving on, they stay, and more white blood cells come in behind them. The accumulation causes damage to internal organs, like the lungs, and can lead to death, reported the study published in the journal 'Cell.'

Sepsis is not the only condition that leads to an unhealthy collection of white blood cells in the lungs. Inflammation caused by injury, and other diseases, can also create this harmful response. Acute lung injury is a leading cause of death in critical care in Canada.

The researchers wanted to know what was causing some cells to bind in the lungs. Senger and Robbins are cancer biologists and were investigating how cancer metastasises. They knew that some cancer cells target the lungs and somehow stay there and grow.

Many people with cancerous tumours do not die from the primary tumour, but rather from where cancer metastasises.

Meanwhile, Kubes, a specialist in inflammation was investigating why white blood cells collect in the lungs. In conditions like sepsis, victims often die from the body's response to the illness, not from sepsis itself.

Together they started screening for a molecule present in both processes. They targeted the lining of blood vessels in the lungs because they suspected a signal would be present that allows cancer cells and white blood cells to stop and collect there.

That's exactly where they found a molecule present during inflammation that could bind with white blood cells and help the cells pass from the bloodstream into the tissue.

As long as those molecules are present, white blood cells continue to bind them.

Once the scientists understood how and why the white blood cells were entering the tissue, they went in search of an "off switch" to stop the molecule from binding with the white blood cell.

The teams developed a drug-like molecule that when introduced into the bloodstream prevents white blood cells from binding with the molecule.

"We discovered that by targeting this molecule we can stop the ill effects of sepsis, acute lung injury, and death. It could have an impact on any inflammatory condition in which lung injury is a contributor to worsening a patient's condition," said Kubes, the director of the Snyder Institute for Chronic Diseases at the CSM and professor in the Department of Physiology and Pharmacology.

With this knowledge, the researchers have found a similar process that occurs in the liver. They've now 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.