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Title: Impact of ageing on macrophage function
Author: Linehan, Eimear
ISNI:       0000 0004 5371 631X
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2014
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available