Patel, Amit Ashok;
(2020)
Human Mononuclear Phagocyte Kinetics in Health and Inflammation.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
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.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Human Mononuclear Phagocyte Kinetics in Health and Inflammation |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10091744 |
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