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fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Languages: English
Types: Doctoral thesis
Subjects:
Individuals within the aged population show an increased susceptibility to infection, implying a decline in immune function, a phenomenon known as immunosenescence. Paradoxically, an increase in autoimmune disease, such as rheumatoid arthritis, is also associated with ageing, therefore some aspects of the immune system appear to be inappropriately active in the elderly. The above evidence suggests inappropriate control of the immune system as we age. Macrophages, and their precursors monocytes, play a key role in control of the immune system. They play an important role in host defence in the form of phagocytosis, and also link the innate and adaptive immune system via antigen presentation. Macrophages also have a reparative role, as professional phagocytes of dead and dying cells. Clearance of apoptotic cells by macrophages has also been shown to directly influence immune responses in an anti-inflammatory manner. Inappropriate control of macrophage function with regards to dead cell clearance may contribute to pathology as we age. The aims of this study were to assess the impact of lipid treatment, as a model of the aged environment, on the ability of macrophages to interact with, and respond to, apoptotic cells. Using a series of in vitro cell models, responses of macrophages (normal and lipid-loaded) to apoptotic macrophages (normal and lipid-loaded) were investigated. Monocyte recruitment to apoptotic cells, a key process in resolving inflammation, was assessed in addition to cytokine responses. Data here shows, for the first time, that apoptotic macrophages (normal and lipid-loaded) induce inflammation in human monocyte-derived macrophages, a response that could drive inflammation in age-associated pathology e.g. atherosclerosis. Monoclonal antibody inhibition studies suggest the classical chemokine CX3CL1 may be involved in monocyte recruitment to apoptotic macrophages, but not apoptotic foam cells, therefore differential clearance strategies may be employed following lipid-loading. CD14, an important apoptotic cell tethering receptor, was not found to have a prominent role in this process, whilst the role for ICAM-3 remains unclear. Additionally, a small pilot study using macrophages from young (<25) and mid-life (>40) donors was undertaken. Preliminary data was gathered to assess the ability of primary human monocyte-derived macrophages, from young and mid-life donors, to interact with, and respond to, apoptotic cells. MØ from mid-life individuals showed no significant differences in their ability to respond to immune modulation by apoptotic cells compared to MØ from young donors. Larger cohorts would be required to investigate whether immune modulation of MØ by apoptotic cells contribute to inflammatory pathology throughout ageing.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • Medawar PB. An Unresolved Problem of Biology. H.K. Lewis, London1952.
    • Holliday R. Aging is No Longer an Unsolved Problem in Biology. Annals of the New York Academy of Sciences. 2006;1067(1):1-9.
    • Solana R, Tarazona R, Gayoso I, Lesur O, Dupuis G, Fulop T. Innate immunosenescence: Effect of aging on cells and receptors of the innate immune system in humans. Seminars in Immunology. 2012;24(5):331-341.
    • Nancy JS. Inflammation in aging: cause, effect, or both? Discov Med. 2012;13(73):451-460.
    • Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol. 2004;5(2):133-139.
    • Gardner ID. The effect of aging on susceptibility to infection. Rev Infect Dis. 1980;2(5):801- 810.
    • Sebastián C, Espia M, Serra M, Celada A, Lloberas J. MacrophAging: A cellular and molecular review. Immunobiology. 2005;210(2-4):121-126.
    • Prelog M. Aging of the immune system: A risk factor for autoimmunity? Autoimmunity Reviews. 2006;5(2):136-139.
    • Tutuncu Z, Kavanaugh A. Rheumatic Disease in the Elderly: Rheumatoid Arthritis. Rheumatic Disease Clinics of North America. 2007;33(1):57-70.
    • Mechanisms of ageing and development. 1984;26(1):83-89.
    • Franceschi C, Bonafe M, Valensin S, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244-254.
    • Franceschi C, Capri M, Monti D, et al. Inflammaging and anti-inflammaging: A systemic perspective on aging and longevity emerged from studies in humans. Mechanisms of Ageing and Development. 2007;128(1):92-105.
    • Weng NP. Aging of the immune system: how much can the adaptive immune system adapt? Immunity. 2006;24(5):495-499.
    • Njemini R, Bautmans I, Onyema O, Van Puyvelde K, Demanet C, Mets T. Circulating Heat Shock Protein 70 in Health, Aging and Disease. BMC Immunology. 2011;12(1):1-8.
    • Zhang X, Mosser D. Macrophage activation by endogenous danger signals. The Journal of Pathology. 2008;214(2):161-178.
    • Mechanisms of Ageing and Development. 2000;117(1-3):57-68.
    • Wang CQ, Udupa KB, Xiao H, Lipschitz DA. Effect of age on marrow macrophage number and function. Aging (Milano). 1995;7(5):379-384.
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