- Atherosclerosis & inflammation: Macrophage heterogeneity in focus
M.P.J. de Winther
- Award date
- 15 May 2014
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
Macrophages characteristically feature a considerable degree of heterogeneity and plasticity to accommodate for the enormous variety in stimuli and challenges that their microenvironment presents them with. By virtue of their activation status, these cells can be classified into one of several subsets with more or less unique effector profiles. The most frequently used nomenclature in this context is the M1/M2 paradigm, which represents extremes in the spectrum of macrophage subsets and has been steadily expanded over the last decade to allow for other subsets to be incorporated (e.g. M1a-b, M2a-c, Mox, Mhem). M1 macrophages are derived from exposure to IFNɣ in the presence or absence of LPS and are uniquely adept at killing intracellular pathogens (as described above) and pro-inflammatory effector functions, characterised by secretion of pro-inflammatory cytokines. M2 macrophages on the other hand include several types of alternative activation that are elicited through IL-4/IL-13, IL-10 and several other mediators. Functionally, these cells are critical to the resolution of (excessive) inflammation, host defense to extracellular parasites and wound healing. With regard to atherosclerosis, due to their pro-inflammatory functions, M1 subsets are hypothesised to aggravate atherosclerosis, while M2 macrophages are expected to attenuate atherosclerotic disease processes. Yet, research addressing the ramifications of polarized macrophage subsets in plaque development is few and far between.
Therefore, the aim of this thesis was to 1) elucidate the functional contribution of macrophage subsets in the development of atherosclerosis and to 2) investigate whether systemic immunomodulation of macrophage subsets can be used to combat atherogenesis.
- Research conducted at: Universiteit van Amsterdam
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