Katharina Buczek
“We are interested in the molecular mechanisms that guide rapid neutrophils accumulation in tissues and hope ultimately to harness them for therapeutic benefit,” Dr. Ma explained.
So, in his team’s most recent study, the researchers sought to investigate the physiological role of 5-oxoETE– an inflammatory lipid that is poorly understood.
On the surface of the neutrophil, this lipid binds to OXER1– an inflammatory molecule. And this binding ultimately promotes the migration and accumulation of neutrophils.
Previous evidence has also suggested that 5-oxoETE is involved in the inflammation of airways prompted by allergic reactions.
However, Dr. Ma simply wanted to understand the lipid’s physiological functions first– which were elusive.
As for why the researchers turned to zebrafish for their study, evolution is to thank.
“While OXER1 is present in humans and in most larger mammals, like cats and monkeys, it is not evolutionarily conserved in mice or rates– which are the most popular animal models for preclinical research. Fish, however, do not have this receptor, and so they make a great model for study,” Dr. Ma said.
The Zebrafish Study
After the researchers infected the ears of zebrafish with a bacteria known as Pseudomonas aeruginosa, they discovered that production of 5-oxoETE and OXER1 began.
This indicated that both were playing a critical role in enabling the fish to fight off the infection.
Then, the researchers turned to zebrafish larvae and manipulated them to lack one functional version of OXER1. The team found that this change caused the fish to frequently become infected– likely because “neutrophils were unable to rally to the infection sites.”
