These peritoneal macrophages can protect the abdomen – or cause a serious surgical side effect.
Dennis Kunkel Microscopy / Science Source
By Mitch Leslie
Abdominal surgeries are exhausting enough. But every year, hundreds of thousands of patients undergo follow-up surgeries to cut away the internal scar tissue that results from it, causing problems such as pain and intestinal blockages. Now, researchers have discovered that protective immune cells, known as macrophages, can cause the accumulation of this scar tissue and offer a possible strategy to stop it.
These post-surgical scars are a big problem, ‘said cell biologist and immunologist Daniel McVicar of the National Cancer Institute, who was not involved in the work. According to him, the study is “working on the cellular mechanism for how this happens.”
Immunologist Paul Kubes of the University of Calgary and colleagues canceled the link between macrophages and the build-up of abdominal scar tissue. They examined the roles of the cells in the fluid-filled peritoneal cavity, which contains organs such as the liver and intestines. Macrophages there, like those elsewhere in the body, bubble bacteria and other microbial invaders. But 5 years ago, the researchers found that the peritoneal cells also heal to promote organ damage.
For the new study, Cubes’ team devised a way to spy on the cells in live mice. The researchers stretched the middle of the abdomen between the stomach muscles of the animals to create a bump like a fracture. The scientists were able to observe the cells’ activities through a strip of translucent tissue in that part of the abdomen.
The team then used a laser to inflict a small burn on the abdominal wall. Macrophages accumulated on the damaged area – hundreds of them showed up within minutes – forming a cap. “We thought it was like ants crawling on the organs,” until the cells find the place where they are needed, Cubes says.
Instead, the peritoneal cells float around and cling to the wounded tissue as they pass. Their style for adjusting the flow makes them different from typical macrophages, which belong on their targets, and more like platelets, the cellular shards that contract at wounds to produce blood clots. The meeting accelerates the recovery of macrophages, the team reported today in Science. When the researchers give the mice a molecule that prevents the cells from accumulating, their injuries become about 50% slower.
“This is a clear and cool example of the role of macrophages in wound healing,” said immunologist David Mosser of the University of Maryland, College Park, who was not linked to the study.
But the macrophages apparently cannot handle the severe tissue trauma caused by surgery. When the team performed abdominal surgery on the mice, the cells arrived at the incision site, stacked in large clumps and braided with sticky protein fibers. This process yielded structures resembling peritoneal adhesions, ligaments of scar tissue that can be painful and sometimes fatal.
In humans, most peritoneal adhesions are due to surgery, and their removal is the motivation for approximately 300,000 surgeries each year in the United States. “I suspect the adhesive is an inappropriate reaction” by the macrophages, Kubes says. He and his team are working closely with medicinal chemists to develop drugs that shrink its formation.
Gwendalyn Randolph, an immunologist at Washington University of Medicine in St. Louis, Missouri. Louis, however, says she’s very skeptical ‘that the team has nailed down the mechanism of how these macrophages heal and harm. To confirm the role of the immune cells, researchers need to test whether adhesions are reduced in genetically modified mice that do not have the cells. Still, she says, the study could boost by stimulating researchers to think more about these surgical complications.