Controlling adhesions in the abdomen

Date:
March 5, 2021
Source:
University of Bern
Summary:
Adhesions are scars in the abdomen, which can occur after surgery,
often have serious consequences. Now, researchers have discovered
how such adhesions form. The findings may help to develop a drug
to prevent adhesions in the future.



FULL STORY ========================================================================== Scars inside the abdomen, known as adhesions, form after inflammation
or surgery. They can cause chronic pain and digestive problems, lead
to infertility in women, or even have potentially life-threatening
consequences such as intestinal obstruction. If adhesions develop,
they must be operated on again. They also make subsequent surgical interventions more difficult. This leads to substantial suffering
for those affected and is also a significant financial burden for the healthcare system. In the USA alone, adhesions in the abdomen result in healthcare costs of 2.3 billion dollars per year.


========================================================================== Knowledge about the cause of adhesions is still incomplete, and there no therapy for them. "Because the disease has been largely overlooked in
research, we have started this program in Bern to find out more about
the development of adhesions," says Daniel Candinas, Co-author of this
study. It had already been suspected that special immune cells, called macrophages, play a decisive role in the development. This was confirmed
by Joel Zindel and Daniel Candinas from the Department of Visceral Surgery
and Medicine at Inselspital and Department for BioMedical Research (DBMR)
at the University of Bern.

Then, Zindel continued his research at the University of Calgary in Canada
in the group led by Paul Kubes, as they are considered world-leading in
the field of macrophages in the abdominal cavity. Thanks to Zindel's
clinical expertise and the Canadian researchers' know-how, it was
possible to develop a new imaging system using cutting-edge microscopy
that allows to see inside the living body. This allowed them to catch
the macrophages in flagrante and on film, as they form shapes that then
lead to the adhesions.

The researchers were also able to describe the molecular mechanisms
behind this. The results of the study have now been published as the
cover story of the journal Science.

New technology developed Macrophages are found in what is called
peritoneal fluid, a lubricant between the peritoneum, which is inner
lining of the abdominal wall, and a similar lining around the organs in
the abdominal cavity. Macrophages passively swim around in this fluid,
much like plankton in the sea. Their tasks include eliminating pathogens,
but also sealing injuries in the abdominal cavity as quickly as possible.



==========================================================================
How they accomplish the latter, i.e., recognizing an injury and moving
there, was unclear until now. Since these cells behave in the test
tube very differently from the way they do in the body, Zindel and
Kubes developed a new microscopy technique that allowed them to use
the thinnest part of the abdominal wall as a window to look into the
peritoneal caity, the "native habitat" of these macrophages and film
them as they move arround.

When macrophages lose control When there is an injury within the
abdominal cavity, macrophages aggregate within minutes to form clot-like structures. In this way, they seal the injury.

As the researchers led by Zindel and Kubes have discovered, the molecular mechanism behind this is based on special, non-specific receptors that recognize a variety of structures. Simply by being moved through the
fluid via respiratory or digestive movement, these receptors act to
initiate clotting around a wound. What works fine for smaller injuries
becomes a problem for large ones, however, such as surgically opening
the abdominal wall, or inserting an implant. "In larger injuries, the macrophages get out of control - - the clots don't stop growing and
form long strands," Zindel explains. "We were able to show that these
strands are what lead to the adhesions." This could have evolutionary
reasons: Macrophages are optimized by evolution to cope well with small injuries. "Let's take the example of a hunter who is injured by a deer
antler," Zindel says. "The macrophages seal all the internal holes
as quickly as possible -- which is the only way to survive." However,
when air enters the abdominal cavity during abdominal surgery or foreign
bodies are implanted, the macrophages are overwhelmed because evolution
has not prepared them for this challenge. "In this case, the macrophages
become harmful and cause adhesions," Zindel explains.

Patent pending The researchers found that when the corresponding
receptors are blocked in mice, it leads to fewer adhesions. Thus, a
patent application has been filed for the use of the active ingredient
against adhesions. The findings are relevant to many areas of research,
as there are no other immune cells which are being recruited as quickly
as macrophages in the abdominal cavity. Similar mechanisms could be
present in other cavities such as the heart or lungs, or could play a
role not only in injuries but also diseases such as abdominal tumors.

"This is an example of how laboratory research has high translational
value," says Daniel Candinas. Together with Calgary, the Bernese
researchers will now look for partners in the industry and are hopeful
that they will be able to confirm the efficacy of the compound in human
tissue as well. In the future, patients could, for example, be given a
drug before surgery that suppresses the macrophage reaction and inhibits
the formation of adhesions.

========================================================================== Story Source: Materials provided by University_of_Bern. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. J. Zindel, M. Peiseler, M. Hossain, C. Deppermann, W. Y. Lee,
B. Haenni,
B. Zuber, J. F. Deniset, B. G. J. Surewaard, D. Candinas, P. Kubes.

Primordial GATA6 macrophages function as extravascular platelets
in sterile injury. Science, 2021 DOI: 10.1126/science.abe0595 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/03/210305113515.htm

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