Macrophages—the big eaters of the immune system—reside in most tissues. They’re plastic, and change their function depending on the environmental cues they receive. Therefore, they play many different roles. Results from a new study highlight one of these new roles, until now unknown—macrophages grab the broken ends of blood vessels and stick them back together.
The study (Macrophages Mediate the Repair of Brain Vascular Rupture through Direct Physical Adhesion and Mechanical Traction) was carried out in zebrafish, which served as model of human brain microbleeds. The occurrence of microbleeds is a pervasive problem in older individuals. “The brains of older people are sometimes peppered with dark splotches where blood vessels have burst and created tiny dead zones of tissue.” In the general population, a high microbleed count is associated with an increased risk for cognitive deterioration and dementia, and appears to mark the presence of neurodegenerative brain damage.
For the study, researchers used lasers to create a clean split with two broken ends in the small blood vessels of the zebrafish brain. Then, through a specialized microscope, they observed what happened after the blood vessels were ruptured. The researchers noticed an unexpected repair process that started about a half hour after they induced the vessel damage. A macrophage showed up, and extended two “arms” from its body toward the ends of a broken blood vessel, using a variety of adhesion molecules to attach itself to the vessel. Then, it pulled the two broken ends together to mediate their repair. The macrophage left the scene after the blood vessel was repaired. The whole process took about three hours.
In addition, the researchers noted that usually only one macrophage arrived at the laser-wound site to mend the broken ends. Rarely, two macrophages arrived at the injury on their own—in these instances, each macrophage grabbed one of the broken ends of the blood vessel. However, the macrophages then disengaged from the vessel without fixing the damage.
Chi Liu, lead author of the study, said in a press release: “At the beginning, we weren’t sure this was a repairing behavior. After we confirmed that the macrophage mediates this repair through direct physical adhesion and generation of mechanical traction forces, we were excited. This is a previously unexpected role of macrophages.”
The researchers observed a similar repair process even for a ruptured blood vessel in the zebrafish fin. After the blood vessel was ruptured using the laser, a macrophage arrived at the injury site and extended its protrusions to pull the broken ends of the blood vessel back together.
Luo added: “Several aspects of vascular development and remodeling, associated with macrophages, are conserved in human and zebrafish. Microglia [a subset of macrophage cells] are required for the repair of blood-brain barrier injury in mice, and macrophages can be found surrounding most capillary microbleeds in humans. We believe that the macrophage repair system in our study is very much likely replicated in humans and mice.”
Watch this video to see how, after cerebrovascular rupture, a macrophage (green) migrates to the lesion, extends protrusions (arrowhead), adheres to and pulls the ends of the blood vessel (orange) together, and finally leaves the lesion when the repair is accomplished. Duration of imaging is 285 minutes.