Fewer abnormal blood vessels (green) grow beneath the retina after injections of young macrophages (top) than old cells (bottom).

APTE

As they age, some cells simply fail to perform their jobs, but macrophages become troublemakers. According to Jennifer Kelly, Rajendra Apte (Washington University, St. Louis, MO), and colleagues, old macrophages promote abnormal blood vessel growth that can lead to diseases such as age-related macular degeneration (AMD).

Ample evidence suggests that macrophages check angiogenesis. Apte and colleagues previously reported that macrophages with Fas ligand (FasL) on their surface spur blood vessel cells to commit suicide, thus pruning new capillaries. But other work indicates that macrophages encourage vessel growth. The researchers wanted to pin down macrophages' effects on angiogenesis during AMD.

The team replicated AMD's key defect—growth of numerous vessels beneath the retina—by zapping the eyes of mice with a laser. Fewer vessels sprouted in young mice than in old animals. Injecting macrophages from young mice into the eyes of older mice curtailed angiogenesis, but macrophages from elderly mice didn't. Older macrophages underwent a character change, altering their cytokine output and producing less FasL. The trigger might be a surge in a known provoker of angiogenesis, interleukin-10.

The aging switch that transforms macrophages from angiogenesis blockers into angiogenesis boosters might contribute to other diseases with overactive vessel growth, including atherosclerosis and cancer.

Reference:

Kelly, J., et al.
2007
.
J. Clin. Invest.
117
:
3421
–3426.