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: We next explored whether the increased NADPH oxidase activity of M1 macrophages was responsible for the maintenance of near-neutral pH in their phagosomes (Figure 1A). Treatment with diphenyleneiodonium (DPI), a potent oxidase inhibitor, unmasked an acidification of phagosomes (Figure 5A). However, despite the absence of oxidase activity, the phagosomes in M1 macrophages acidified more slowly than those in M2 cells (Figure 5A). Thus factors other than the rate of proton consumption by dismutation of superoxide must contribute to the differential behavior of M1 and M2 phagosomes.
Affiliation: Program in Cell Biology, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.