Finding out why immune cells cause injury to normal tissues
A gene in certain white blood cells is discovered to provoke a prolonged
immune response leading to tissue damage
TORONTO, May 18 /CNW/ - Toronto General Hospital researchers have
discovered that a gene turned on in white blood cells known as neutrophils may
play an important role in sepsis, a serious illness caused by the body's
response to life-threatening infection.
This finding paves the way for therapies that can turn off excessive
inflammation, although treatments for patients are years away.
"We have discovered an important piece of the puzzle of why inflammation
isn't turned off at the appropriate time and instead continues to attack the
body," says Dr. John Marshall, a surgeon and critical care physician at
Toronto General Hospital of the University Health Network and Professor of
Surgery at University of Toronto. The research is published in the May edition
of the Journal of Clinical Investigation.
In their research, Dr. Marshall and Dr. Songhui Jia, a research associate
who co-authored the paper, examined the neutrophils of critically ill patients
in an intensive care unit at Toronto General Hospital. These blood cells were
then compared to the blood cells of a control group of volunteers who were
healthy. The researchers found that the critically ill patients had elevated
levels of the activated neutrophils in comparison to the healthy volunteers.
White blood cells known as neutrophils are continually on the lookout for
invading bacteria, and attack them once they have found them. Neutrophils are
produced in large numbers in response to infection, trauma or other stimuli.
When neutrophils encounter bacteria or injured tissue, they attack
indiscriminately, destroying the invading bacteria or other foreign
substances, and harming normal tissues at the same time. This process produces
the familiar signs of inflammation that occur, for example, with a boil.
Neutrophils typically live for less than a day, and when the cells die, the
inflammatory reaction stops.
What the Toronto General Hospital scientists discovered was the mechanism
by which neutrophils subvert their own death, and so cause damage to healthy
tissue.
These white blood cells survive because a gene, called Pre-B cell
colony-enhancing factor (PBEF), is turned on in response to stimuli from the
bacteria and the surrounding inflammation. PBEF blocks neutrophil cell death,
with the result that the inflammatory response continues, injuring normal
tissue in the immediate environment. However, the researchers found that when
they blocked PBEF in neutrophils from critically ill patients with sepsis, the
cells died and the inflammatory response then stopped.
Targeting PBEF could eventually result in a potential therapy for
patients who have diseases resulting from excessive inflammation, such as
arthritis or sepsis.
"Currently, we have very few therapies for sepsis," says Dr. Marshall,
pointing out that the illness affects almost 800,000 North Americans each
year, resulting in more than 200,000 deaths annually, and is the leading cause
of death in intensive care units.
Antibiotics, explains Dr. Marshall, can kill bacteria or stop them from
growing. But they do not prevent the neutrophils from continuing to ravage
healthy body tissue. "We are excited about the prospect that targeting PBEF
might hasten the death of neutrophils and prevent them from damaging healthy
body tissue such as lungs or kidneys."
While previous attempts to treat sepsis by blocking inflammation have
been disappointing, Dr. Marshall believes that PBEF may be a more promising
target. PBEF is produced at a later time period, and only after the patient
begins showing clinical symptoms of infection, so there is a wider therapeutic
window of opportunity for interventions.
This research was supported by grants from the Canadian Institutes of
Health Research.
Toronto General Hospital is a partner in University Health Network, along
with Toronto Western and Princess Margaret Hospitals. The scope of research
and complexity of cases at Toronto General Hospital has made it a national and
international source for discovery, education and patient care. It has one of
the largest hospital-based research programs in Canada, with major research
projects in cardiology, transplantation, surgical innovation, infectious
diseases, and genomic medicine. Toronto General Hospital is a teaching
hospital affiliated with the University of Toronto.
For further information: please contact: Alex Radkewycz, TGH Public
Affairs, (416) 340-3895 |
