A Macrophage is a type of specialized white blood cell. These cells are mostly concerned with the inflammatory response; they increase or decrease the inflammation depending on the signal they get.
When signaled to increase inflammation, they are quite handy for kicking pathogen butts trying to settle in the body and cause an infection. And after a while, when the waters look clear, they are signaled once more to cut it with the pro-inflammatory response. This regulated response helps fend off infections and promotes tissue repair as it subsides.
Though in some cases, the body doesn't want to - or can't - let go of the inflammatory response, leading to excessive and dangerous levels of inflammation. Examples of this include autoimmune diseases (ie. type 1 diabetes, aplastic anemia, multiple sclerosis) and Acute Respiratory Distress Syndrome (ARDS) which seems more prevalent these days due to COVID-19.
A research group at the University of Illinois, Chicago (UIC) recently found that the programming of macrophages is more complex than we thought previously. Their study focusing on macrophage programming on animal models of lung injury is published on Nature Immunology.
Lead author Asrar Malik, the UIC Schweppe Family Distinguished Professor and head of pharmacology and regenerative medicine at the College of Medicine explained to UIC Today: "We found that macrophage programming is driven by more than the immune system — it is also driven by the environment in which the macrophages reside".
The majority of lung injuries heal pretty much just fine, but some patients develop severe lung injury.
Dr. Jalees Rehman, UIC professor of medicine and pharmacology and regenerative medicine and co-lead author of the paper took over and added "We demonstrated that lung endothelial cells — which are the cells that line blood vessels — are essential in programming macrophages with potent tissue-reparative and anti-inflammatory functions."
To figure out what's going on, the team analyzed the proteins released by blood vessel walls. These proteins act as chemical signals and the team found that a specific protein called Rspondin3 was released in bulk during the inflammatory response against injury.
Bisheng Zhoue, the first author of the study, who is a UIC research assistant of pharmacology and regenerative medicine said "When we removed the gene responsible for Rspondin3 from the blood vessel endothelial cells, we observed that macrophages did not decelerate inflammation. Instead, the lungs became more injured."
The testing was repeated on multiple models and the results were consistent, confirming that the blood vessels play a crucial role in instructing macrophages to do stuff.
Rehman noted that although the study was focused on lung injuries, the findings could also prove useful in diseases in other organs. The brain, liver, heart, and intestines are other organs at risk of excessive immune response in the event of a disrupted inflammatory response balance.