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Macrophages can be thought of as a dispersed homeostatic organ
Tissue macrophages constitute a distributed mononuclear phagocyte cellular system (MPS), contributing to the body’s responses to physiologic changes and to infectious challenge; thus, the MPS is comparable to the nervous and endocrine systems, in that it is adaptable, regulated and able to perform trophic [1] as well as defence functions, locally and systemically. Local macrophages induce tissue-specific metabolic responses such as hepatocyte biosynthesis of plasma proteins that provide an early response to infection in the acute phase reaction, and initiate features of systemic inflammation and infection such as loss of appetite and tissue catabolism [2]. The dual nature of macrophage functions, host protection versus tissue injury, is maintained in a fine balance; broadly, macrophage phagocytosis, clearance and secretion contribute to innate and adaptive defences against infection and underpin the process of inflammation, while the same processes, but with distinct secreted signals, restore tissue homeostasis and promote subsequent repair. Myeloid cells of the MPS interact with cells of the lymphoid system at many levels, recognition of non-self or modified self-antigens, initiating cellular and antibody immune responses, while executing effector functions which, if excessive or perpetuated, bring about tissue destruction. Monocyte migration and widespread tissue distribution provide portals for microbial dissemination, as well as host protection. During malignancy, tissue macrophages play an important role in promoting the survival, growth and spread of tumour cells [3].
Reflecting their ancient evolutionary origin, macrophage-like cells are found in many multicellular organisms, as motile, wandering cells performing a range of housekeeping, digestive and defence functions [4]. Even in their absence, in Caenorhabditis elegans, for example, other cells express comparable phagocytic functions. Elie Metchnikoff, immunology Nobel laureate of 1908 together with Paul Ehrlich, discovered macrophages in 1882 through experiments with simple marine invertebrates, where he recognized them as phagocytes able to respond to foreign particles and infection by a process analogous to inflammation in higher organisms [5]. This reputed “Eureka discovery” marked his transformation from comparative zoologist to experimental pathologist. His successors over the century since his death in 1916, appreciating that macrophages provided a widely distributed clearance system for particulates, coined the term reticulo-endothelial system (RES) for them-“reticular” because they are a network of cells, and “endothelial” because of particle uptake...