Macrophage Activation Downregulates the Degradative Capacity of the Phagosome

@article{Yates2007MacrophageAD,
  title={Macrophage Activation Downregulates the Degradative Capacity of the Phagosome},
  author={Robin M. Yates and Albin Hermetter and Gregory A. Taylor and David G. Russell},
  journal={Traffic},
  year={2007},
  volume={8}
}
The phagosome is key to most macrophage functions. It is the site of degradation of particulate material, of bacterial killing and the generation of peptides for antigen presentation. Despite its role at the fulcrum of the innate and acquired immune systems, little is known about the physiology of this organelle in activated macrophages. In this study, we utilize fluorometric techniques to characterize functional alterations in the lumenal environment of the maturing phagosome following… 
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References

SHOWING 1-10 OF 38 REFERENCES
The Kinetics of Phagosome Maturation as a Function of Phagosome/Lysosome Fusion and Acquisition of Hydrolytic Activity
TLDR
Three novel assays that quantify important biological properties of the phagosome as it matures are described, demonstrating the veracity, sensitivity and versatility of the assays.
Cytokine activation leads to acidification and increases maturation of Mycobacterium avium-containing phagosomes in murine macrophages.
TLDR
It is demonstrated that bacteriostatic and bactericidal activities of activated macrophages are concomitant with alterations in the physiology of the mycobacterial phagosome.
Analysis of Protease Activity in Live Antigen-presenting Cells Shows Regulation of the Phagosomal Proteolytic Contents During Dendritic Cell Activation
TLDR
It is found that an ingested particle sequentially encounters distinct protease activities during phagosomal maturation, which is a tightly regulated process that varies according to the type and differentiation stage of the phagocyte.
Lysosomal Enzyme Trafficking between Phagosomes, Endosomes, and Lysosomes in J774 Macrophages
TLDR
The organelles usually referred to as “lysosomes” in fact encompass a growing family of highly dynamic but functionally distinct endocytic organellES.
Altered membrane trafficking in activated bone marrow‐derived macrophages
TLDR
One consequence of this slowed membrane trafficking in activated macrophages was a prolonged exposure of incoming molecules to an acidic nonlysosomal compartment, a condition which may facilitate microbicidal chemistries or antigen processing.
Isolation of Mycobacterium tuberculosis mutants defective in the arrest of phagosome maturation.
TLDR
A genetic screen is developed that facilitates the isolation of mutants defective in arresting the maturation of their phagosomes from a library of transposon-mutagenized bacteria and clarifies the processes active in modulation of phagosome biogenesis by M. tuberculosis.
Regulation of Phagosomal Acidification
TLDR
Investigation of whether Na+/H+ exchange (NHE) contributes to phagosomal acidification found that NHE1 is the predominant isoform of the exchanger in macrophages, and measurements of pH indicated that it is functional in this location.
The uniformity of phagosome maturation in macrophages
TLDR
The two patterns of PI(3)P on otherwise identical phagosomes indicated that organelle maturation does not necessarily follow a single path and that some features of phagosome maturation are integrated over the entire organelle.
...
1
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