Restoring appropriate movement to immune cells may save seriously burned patients

June 19, 2013

Advances in emergency medicine and trauma surgery have had a significant impact on survival of patients in the days immediately after major injuries, including burns. Patients who survive the immediate aftermath of their injuries now are at greatest risk from infections – particularly the overwhelming, life-threatening immune reaction known as sepsis – or from inflammation-induced multiorgan failure. Now, a device developed by Massachusetts General Hospital (MGH) investigators that measures the movement of key immune cells may help determine which patients are at greatest risk for complications, and a novel treatment that directly addresses the cause of such complications could prevent many associated deaths.

"One in every three patients with burn injuries that dies in an does so because of septic complications," says Daniel Irimia, MD, PhD, of the MGH Department of Surgery, corresponding author of a report in the June FASEB Journal. "In the days immediately after injury, called neutrophils can lose their ability to move to the site of an injury. In an animal model of burn injury, we found that death due to septic complications can be prevented by a treatment that restores the proper movement of neutrophils."

The most abundant type of white blood cell, neutrophils are part of the and the body's first line of defense against infections. Normally, neutrophils are drawn towards the site of a infection by from bacteria or injured cells. However, it has recently been discovered that – in patients with serious burn injuries – neutrophils' ability to follow these signals becomes impaired soon after the injury. Not only does that impairment reduce the availability of the cells to fight infection at the site of injury, but misguided neutrophils also can attack healthy tissue, contributing to . The current study was designed to analyze changes in the speed and direction of neutrophil movement after burn injury and to investigate whether recently identified molecules called resolvins, which normally act to terminate the inflammatory process after an infection has cleared, could also restore normal neutrophil motion after burns.

Using a microfluidic device that measures neutrophil movement developed at the MGH BioMEMS Resource Center, the investigators first confirmed that the ability of neutrophils from burn-injured rats to move towards a chemical signal of injury progressively deteriorates – in both speed and accuracy – as time passes. While cells from uninjured animals moved quickly and directly through a series of microchannels towards the injury signal, cells from blood samples taken 9 days after the injury became trapped in the device or reversed direction. The researchers then showed that application of resolvin D2 significantly improved the in vitro migratory ability of from burned animals.

Experiments in living rats revealed that treatment with resolvin D2 restored appropriate neutrophil motion, an effect that lasted at least two days after treatment ended. In addition, when burn-injured animals were subjected to a second sepsis-inducing injury, treatment with resolvin D2 significantly increased survival. For example, in a group of rats injected with a bacterial toxin nine days after a burn injury, all of those pre-treated with resolvin survived, while all untreated animals died.

"Our ability to measure neutrophil movement in great detail gave us the information we needed to develop the optimal dosage and duration of resolvin treatment for the burned rats. Our results also indicate that neutrophil motility could be a useful biomarker for the actual risk of septic complications in patients," says Irimia, an assistant professor of Surgery at Harvard Medical School who is also affiliated with Shriner's Hospital for Children. "Our experiments in the animal model suggest that a resolvin-based treatment could prevent those complications by restoring the body's own resources, allowing it to respond to secondary infections, which could save hundreds of patients with burns every year. "

Explore further: Rogue blood cells may contribute to post-surgery organ damage

Related Stories

Rogue blood cells may contribute to post-surgery organ damage

June 26, 2011

A study from scientists at Queen Mary, University of London, sheds new light on why people who experience serious trauma or go through major surgery, can suffer organ damage in parts of the body which are seemingly unconnected ...

Recommended for you

We've all got a blind spot, but it can be shrunk

August 31, 2015

You've probably never noticed, but the human eye includes an unavoidable blind spot. That's because the optic nerve that sends visual signals to the brain must pass through the retina, which creates a hole in that light-sensitive ...

Biologists identify mechanisms of embryonic wound repair

August 31, 2015

It's like something out of a science-fiction movie - time-lapse photography showing how wounds in embryos of fruit flies heal themselves. The images are not only real; they shed light on ways to improve wound recovery in ...

New 'Tissue Velcro' could help repair damaged hearts

August 28, 2015

Engineers at the University of Toronto just made assembling functional heart tissue as easy as fastening your shoes. The team has created a biocompatible scaffold that allows sheets of beating heart cells to snap together ...

Fertilization discovery: Do sperm wield tiny harpoons?

August 26, 2015

Could the sperm harpoon the egg to facilitate fertilization? That's the intriguing possibility raised by the University of Virginia School of Medicine's discovery that a protein within the head of the sperm forms spiky filaments, ...

Research identifies protein that regulates body clock

August 26, 2015

New research into circadian rhythms by researchers at the University of Toronto Mississauga shows that the GRK2 protein plays a major role in regulating the body's internal clock and points the way to remedies for jet lag ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.