title: Aging impairs peritoneal but not bone marrow-derived macrophage phagocytosis.
abstract: Aging results in deterioration of the immune system, which is associated with increased susceptibility to infection and impaired wound healing in the elderly. Phagocytosis is an essential process in both wound healing and immune defence. As such, age-related impairments in phagocytosis impact on the health of the elderly population. Phagocytic efficiency in peritoneal macrophages, bone marrow-derived macrophages and bone marrow monocytes from young and old mice was investigated. Aging significantly impaired phagocytosis by peritoneal macrophages, both in vitro and in vivo. However, bone marrow-derived macrophages and bone marrow monocytes did not exhibit age-related impairments in phagocytosis, suggesting no intrinsic defect in these cells. We sought to investigate underlying mechanisms in age-related impairments in phagocytosis by peritoneal macrophages. We hypothesized that microenvironmental factors in the peritoneum of old mice impaired macrophage phagocytosis. Indeed, macrophages from young mice injected into the peritoneum of old mice exhibited impaired phagocytosis. Proportions of peritoneal immune cells were characterized, and striking increases in numbers of T cells, B1 and B2 cells were observed in the peritoneum of old mice compared with young mice. In addition, B cell-derived IL-10 was increased in resting and LPS-activated peritoneal cell cultures from old mice. These data demonstrate that aging impairs phagocytosis by tissue-resident peritoneal macrophages, but not by bone marrow-derived macrophages/monocytes, and suggest that age-related defects in macrophage phagocytosis may be due to extrinsic factors in the tissue microenvironment. As such, defects may be reversible and macrophages could be targeted therapeutically in order to boost immune function in the elderly.
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7AE, Northern Ireland.
authors.forename: Eimear
authors.initials: E
authors.lastname: Linehan
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Dombrowski
authors.forename: Rachel
authors.initials: R
authors.lastname: Snoddy
authors.forename: Padraic G
authors.initials: PG
authors.lastname: Fallon
authors.forename: Adrien
authors.initials: A
authors.lastname: Kissenpfennig
authors.forename: Denise C
authors.initials: DC
authors.lastname: Fitzgerald
mesh_terms: D000375:Aging / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D002454:Cell Differentiation; D060833:Cellular Microenvironment; D005453:Fluorescence; D017737:Macrophages, Peritoneal / Q000473:pathology*; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000473:pathology; D010587:Phagocytosis / Q000276:immunology*
keywords: aging; bone marrow; immunity; macrophage; peritoneum; phagocytosis