Contrasting phagosome pH regulation and maturation in human M1 and M2 macrophages.
Bottom Line: The paucity of V-ATPases in M1 phagosomes was associated with, and likely caused by, delayed fusion with late endosomes and lysosomes.The delayed kinetics of maturation was, in turn, promoted by the failure of M1 phagosomes to acidify.By contrast, M2 phagosomes proceed to acidify immediately in order to clear apoptotic bodies rapidly and effectively.
Affiliation: Program in Cell Biology, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.Show MeSH
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Mentions: The rate and extent of deposition of formazan were considerably greater in M1 than in M2 phagosomes (Figure 2A). In fact, while formazan deposits were readily observed in M1 phagosomes when using 1 μg/ml NBT, they were only visible in a fraction of M2 phagosomes even when using a 10-fold higher concentration (10 μg/ml) of NBT (Figure 2A). The large difference in reactive oxygen species (ROS) generation was verified using luminol, adding superoxide dismutase and catalase 10 min after phagocytosis was initiated to selectively analyze intracellular (largely intraphagosomal) ROS generation (Dahlgren et al., 2007). As illustrated in Figure 2, B and C, ROS production was much greater and more sustained in M1 than in M2 phagosomes, in good agreement with the formazan deposition determinations.
Affiliation: Program in Cell Biology, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.