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: Whereas the phagosomal pH in M1 macrophages was routinely more alkaline than that of M2 macrophages, it was not constant over time. The variability, which is discernible in the averaged results illustrated in Figure 1A (replicated for reference in Supplemental Figure S4A), becomes more manifest when individual experiments are displayed (Supplemental Figure S4A). Such pH oscillations were unique to M1 phagosomes, as they were never observed in M2 phagosomes (Supplemental Figure S5A). Because fluorescein is best suited for pH measurements near its pKa (6.3), we confirmed the occurrence of oscillations near and above neutral pH using SOZ covalently labeled with SNARF1 (pKa = 7.5), a fluorophore better suited for pH determinations in the alkaline range (Figure 6A).
Affiliation: Program in Cell Biology, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.