Title:
|
Impact of ageing on macrophage function
|
Ageing results in deterioration of the immune system which is associated with increased susceptibility
to infection and impaired tissue regeneration. Phagocytosis by macrophages plays an essential role in
both immune defence and regenerative processes such as repair of myelin sheaths in the CNS
(remyelination). As such, age-related impairments in phagocytosis are likely to impact on the health
of the elderly population. We hypothesised that ageing impaired phagocytosis by macrophages.
Phagocytosis of fluorescent particles by peritoneal macrophages, bone marrow-derived macrophages
and bone marrow monocytes was assessed. Ageing impaired phagocytosis by peritoneal macrophages.
Bone marrow-derived macrophages and bone marrow monocytes did not exhibit age-related
impairments in phagocytosis, indicating that there was no intrinsic defect in the phagocytic capacity
of myeloid progenitors.
We hypothesised that environmental factors in the peritoneum of old mice suppressed macrophage
phagocytosis. Indeed, macrophages from young mice injected into the peritoneum of old mice
exhibited impaired phagocytosis. This provides insight into the underlying cause of age-related
reduction in phagocytosis by peritoneal macrophages. We observed a significant increase in B cells
and B cell-derived IL-I 0 was found. These factors could potentially play a role in the impairment of
phagocytosis by peritoneal macrophages in old mice.
Myelin debris clearance is essential for efficient remyelination to occur. Ageing impaired
phagocytosis of myelin debris by both peritoneal macrophages and CNS-derived microglia. As such,
age-related decline in remyelination efficiency could be in part due to a lack of myelin debris
clearance by macrophages and microglia.
Age-related impairments in phagocytosis by tissue-resident macrophages such as peritoneal
macrophages and microglia have implications for defence against infection, regenerative processes
and also maintenance of homeostasis in the older population. As such, boosting macrophage
phagocytosis may represent an important therapeutic target in order to maintain health in the older
population.
|