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Variations in the Phagosomal Environment of Human Neutrophils and Mononuclear Phagocyte Subsets

Foote, JR; Patel, AA; Yana, S; Segal, AW; (2019) Variations in the Phagosomal Environment of Human Neutrophils and Mononuclear Phagocyte Subsets. Frontiers in Immunology , 10 , Article 188. 10.3389/fimmu.2019.00188. Green open access

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Abstract

The phagosome microenvironment maintains enzyme activity and function. Here we compared the phagosomal pH of human neutrophils, monocytes, dendritic cells (DC), and monocyte-derived cells. An unexpected observation was the striking difference in phagosomal environment between the three monocytes subsets. Classical monocytes and neutrophils exhibited alkaline phagosomes, yet non-classical monocytes had more acidic phagosomes, while intermediate monocytes had a phenotype in-between. We next investigated the differences between primary naïve DC vs. in vitro monocyte-derived DC (MoDC) and established that both these cells had acidic phagosomal environments. Across all phagocytes, alkalinization was dependent upon the activity of the NADPH oxidase activity, demonstrated by the absence of NADPH oxidase from a patient with chronic granulomatous disease (CGD) or the use of a pharmacological inhibitor, diphenylene iodonium (DPI). Interestingly, MoDC stimulated with bacterial lipopolysaccharide had increased phagosomal pH. Overall, the increase in alkalinity within the phagosome was associated with increased oxidase activity. These data highlight the heterogeneous nature and potential function of phagocytic vacuoles within the family of mononuclear phagocytes.

Type: Article
Title: Variations in the Phagosomal Environment of Human Neutrophils and Mononuclear Phagocyte Subsets
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2019.00188
Publisher version: https://doi.org/10.3389/fimmu.2019.00188
Language: English
Additional information: Copyright © 2019 Foote, Patel, Yona and Segal. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: neutrophil, monocyte, macrophage, dendritic cell, phagocytosis, pH, lysosome, NOX2
UCL classification: UCL
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/10075619
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