The study, led by first author Judy Chen, the Eliza Maria Mosher Collegiate Professor in Internal Medicine and Professor of Microbiology and Immunology, and their team, investigates why cells called alveolar macrophages, the first line of defense in the lungs, appear to be compromised with age.
These macrophages are immune cells that target invaders like the flu virus and live in the little air sacs, or alveoli, inside the lungs. Importantly, these cells appear to be lost with age.
Another study found that when macrophages from an aged mouse were transplanted into a young mouse, the cells looked young again. "This led us to conclude that something in the lungs' environment was contributing to this," Chen explained.
Prostaglandin E2 (PGE2), a lipid immune modulator with wide-ranging effects ranging from labor induction in pregnancy to arthritic inflammation, was implicated. The researchers discovered that PGE2 levels in the lungs increase with aging. This increase in PGE2, according to Chen, affects lung macrophages, decreasing their general health and ability to produce.
The team suspects that the buildup of PGE2 is yet another marker of a biological process called senescence, which is often seen with age. Senescence serves as insurance against the runaway division of damaged cells; cells that are senescent are no longer able to replicate.
"One of the intriguing things about these cells is they secrete a lot of inflammatory factors," said Chen.
The study indicated that with age, the cells lining the air sacs in the lungs become senescent, and these cells lead to increased production of PGE2 and inhibition of the immunological response.
They injected aged mice with a medication that disables a PGE2 receptor to evaluate the relationship between PGE2 and greater susceptibility to influenza. "The aged mice that had that treatment had more alveolar macrophages and survived influenza infection better than the older animals that didn't get the therapy," Chen explained.
The researchers will now look into how PGE2 impacts lung macrophages and its possible function in inflammation throughout the body. "As we age, we become more vulnerable not only to influenza, but also to other infections, malignancies, and autoimmune illnesses."
