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.
Highlights
The ability to internalize particles is an evolutionary conserved process
We investigated the differences between primary naïve dendritic cells (DC) vs. in vitro monocyte-derived DC (MoDC) and established that both these cells had acidic phagosomal environments
The phagosome in professional phagocytes falls into two main categories, pathogen killing and digestion, or antigen processing, and presentation
Summary
The ability to internalize particles is an evolutionary conserved process. The downstream purpose of this process varies, from a simple feeding mechanism to a fundamental component of host defense. Within the professional phagocyte family of cells, neutrophils, macrophages, and monocyte-derived cells predominantly kill and digest microbes, whereas dendritic cells (DC) are principally involved in antigen presentation. Because all these cells are phagocytic in nature, many of their primary functions are conducted within the phagocytic vacuole, it is critical to understand each cell’s phagosomal microenvironment and function. Previous studies in neutrophils demonstrated that their phagosomal pH is elevated between 8.5 and 9 for at least 30 min following phagocytosis [1, 2] This alkalinization together with the influx of potassium ions [3] activates the neutral proteases released from cytoplasmic granules that kill and digest the ingested pathogen. Superoxide is transported by NOX2 into the phagosome where it forms products such as H2O2 and H20, consuming protons [1]
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