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

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 sub...

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Main Authors: Juliet R. Foote, Amit A. Patel, Simon Yona, Anthony W. Segal
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2019.00188/full
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author Juliet R. Foote
Amit A. Patel
Simon Yona
Anthony W. Segal
author_facet Juliet R. Foote
Amit A. Patel
Simon Yona
Anthony W. Segal
author_sort Juliet R. Foote
collection DOAJ
description 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.
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spelling doaj.art-07d694d74ac24902beca50a34a73a0802022-12-21T17:58:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-03-011010.3389/fimmu.2019.00188426014Variations in the Phagosomal Environment of Human Neutrophils and Mononuclear Phagocyte SubsetsJuliet R. FooteAmit A. PatelSimon YonaAnthony W. SegalThe 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.00188/fullneutrophilmonocytemacrophagedendritic cellphagocytosispH
spellingShingle Juliet R. Foote
Amit A. Patel
Simon Yona
Anthony W. Segal
Variations in the Phagosomal Environment of Human Neutrophils and Mononuclear Phagocyte Subsets
Frontiers in Immunology
neutrophil
monocyte
macrophage
dendritic cell
phagocytosis
pH
title Variations in the Phagosomal Environment of Human Neutrophils and Mononuclear Phagocyte Subsets
title_full Variations in the Phagosomal Environment of Human Neutrophils and Mononuclear Phagocyte Subsets
title_fullStr Variations in the Phagosomal Environment of Human Neutrophils and Mononuclear Phagocyte Subsets
title_full_unstemmed Variations in the Phagosomal Environment of Human Neutrophils and Mononuclear Phagocyte Subsets
title_short Variations in the Phagosomal Environment of Human Neutrophils and Mononuclear Phagocyte Subsets
title_sort variations in the phagosomal environment of human neutrophils and mononuclear phagocyte subsets
topic neutrophil
monocyte
macrophage
dendritic cell
phagocytosis
pH
url https://www.frontiersin.org/article/10.3389/fimmu.2019.00188/full
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