Researchers at the University of Michigan in Ann Arbor have developed a rod-shaped particle that may stop the body’s fatal immune system overreaction to COVID-19.
The overreaction is the most common cause of death for COVID-19 patients, and a white blood cell may be central to this response. Researchers at the University of Michigan found that rod-shaped particles can prevent the white blood cells from attacking the body by acting as an intruder and distracting the cells.
The No. 1 cause of death for COVID-19 patients is when their lungs fill with fluid, which is called acute respiratory distress syndrome, a manifestation of a condition known as cytokine storm, in which the immune system overreacts and begins attacking the person’s own organs. When this happens in COVID-19 patients, white blood cells break down lung tissue and cause the fluid buildup.
The leading white blood cell is a type called the neutrophil, which makes up 60-70 percent of the cells that usually eat intruder cells in humans.
“They’re like the Coast Guard – their main job is to make sure your boundaries aren’t breached,” says Lola Eniola-Adefeso, leader of the research and university diversity and social transformation professor and a professor of chemical engineering, biomedical engineering, and macromolecular science and engineering.
Neutrophils aren’t specialized, so they can respond to many threats. However, this also means that they don’t always know when to stop attacking.
“As long as there’s cues, neutrophils keep acting. In some instances, the feedback loop is broken, and that turns what is meant to be a good response into a bad response,” Eniola-Adefeso says.
Sometimes, the cells emit molecules that tell cells to break down their barriers and let blood and fluid into a problem site. When the response becomes too much, the cells need to be stopped so other cells can repair the damage.
Previously, Eniola-Adefeso’s group showed that plastic microparticles injected into the blood of mice could distract the white blood cells, acting as a decoy that the white blood cells go after to grab instead. They busily take the particles to the liver to dispose of and don’t focus on inflamed lungs.
Any type of white blood cell that also removes or eats intruders try to attack and get rid of spherical particles, which means other parts of the immune response, including the good parts, might also become distracted. However, only neutrophils are attracted to rod-shaped particles, leaving other white blood cells to do their jobs. While 80 percent of neutrophils attacked the rods, only 5-10 percent of the other white blood cells did.
The team is exploring whether the particles can be made from medications instead of plastic, and Eniola-Adefeso is working with the U-M Office of Technology Transfer to advance her delivery system toward clinical trials. U-M has applied for patent protection and has launched a startup company called Asalyxa.
The findings were published in a paper titled “Neutrophils preferentially phagocytose elongated particles – opportunity for selective targeting in acute inflammatory diseases,” and are in Science Advances.
The research was funded by the Falk Medical Research Trust, the National Institutes of Health, and the University of Michigan.
