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Human Mononuclear Phagocyte Kinetics in Health and Inflammation

出版	University College London, 2020
URL	http://books.google.com.hk/books?id=nGl10AEACAAJ&hl=&source=gbs_api

註釋The mononuclear phagocyte system comprises three types of cells:: monocytes, macrophages and dendritic cells (DC). The kinetics underlying their generation, differentiation and disappearance are critical to understanding how these cells maintain tissue homeostasis as well as orchestrating the immune response. Currently, the circulating kinetics of these cells remain unknown in humans. The kinetic profiles of circulating monocyte subsets (classical, intermediate and non-classical) and DC subsets (pDC, pre-DC, cDC1 and cDC2) were examined in humans for the first time using stable isotope labelling in the form of deuterated glucose. Monocyte subsets appeared sequentially in the circulation which was demonstrated to be due to a developmental relationship between these cells. Pre-DC and cDC appeared prior to monocytes whereas pDC were observed later. After establishing the turnover of circulating mononuclear phagocytes under steady physiological conditions, the kinetics were then examined following experimental human endotoxemia. A temporary loss of circulating mononuclear phagocytes was observed at early time points, classical monocytes were the first to re-appear within the circulation due to an early emergency release from the bone marrow. Finally, in a human model of local inflammation, the infiltrating kinetics of monocyte and DC subsets were examined in the skin. Particularly, pre-DC were observed at higher concentrations compared to the blood which also expressed co-stimulatory molecules (CD80 and CD86). The infiltration of novel cDC2 subsets was also observed. In summary, this thesis illustrates the kinetic and developmental profiles of human mononuclear phagocytes under steady-state and experimental inflammation.