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Updated: Sep 13, 2026
In Vitro Phagocytosis of Myelin Debris by Bone Marrow-Derived Macrophages
Published on: December 30, 2017
Clearance of neutrophil-derived myeloperoxidase by the macrophage mannose receptor
1Veterans Administration Medical Center, Memphis, Tennessee.
Abstract:
Uptake of neutrophil-derived myeloperoxidase by the macrophage mannose receptor was studied. Rat bone marrow-derived macrophages internalized 75% of [125I]myeloperoxidase through a mannose-specific process. Uptake via the mannose receptor is highly sensitive to treatment with oxidants. Treatment of rat macrophages with 1 mM H2O2 for 30 min resulted in a 94% reduction in uptake of myeloperoxidase. By Percoll gradient fractionation studies, 38% of internalized myeloperoxidase was delivered to the lysosomal compartment during a 15-min chase period, similar to findings for delivery of other ligands for this receptor. Once in the lysosome, the myeloperoxidase remained enzymatically active for several hours, with 50% activity remaining at 8 h. Finally, myeloperoxidase-containing macrophages had an increased capacity to down-regulate their own mannose receptors or receptors on neighboring macrophages, possibly through the myeloperoxidase-mediated production of oxidized halogens. Thus, the macrophage mannose receptor plays a potentially physiologic role in regulating extracellular myeloperoxidase levels. The receptor-mediated uptake may either arm the macrophage to contribute to oxidant-mediated tissue damage or may function to clear extracellular myeloperoxidase during the resolution phase of the inflammatory process.
Insights
Macrophages use the mannose receptor to internalize neutrophil myeloperoxidase (MPO). This uptake is reduced by oxidants and delivers active MPO to lysosomes, influencing inflammation.
Area of Science:
- Immunology
- Cell Biology
Background:
- Neutrophil myeloperoxidase (MPO) is a key enzyme in host defense.
- Macrophages express mannose receptors involved in cellular uptake.
- The interaction between MPO and macrophage mannose receptors is not fully understood.
Purpose of the Study:
- To investigate the uptake of neutrophil-derived myeloperoxidase (MPO) by the macrophage mannose receptor.
- To determine the functional consequences of this uptake for macrophages and the inflammatory process.
Main Methods:
- Utilized rat bone marrow-derived macrophages and radiolabeled [125I]myeloperoxidase.
- Assessed MPO uptake via mannose-specific processes and its sensitivity to oxidants (H2O2).
- Employed Percoll gradient fractionation to track lysosomal delivery and measured MPO enzymatic activity over time.
Main Results:
- Macrophages internalized 75% of MPO through a mannose-specific pathway.
- Oxidant treatment (1 mM H2O2) reduced MPO uptake by 94%.
- Internalized MPO reached lysosomes within 15 minutes and remained active for hours; macrophages modulated mannose receptor expression post-uptake.
Conclusions:
- The macrophage mannose receptor mediates the uptake of extracellular myeloperoxidase (MPO).
- This process is sensitive to oxidative stress and influences macrophage receptor regulation.
- Macrophage MPO uptake may contribute to oxidant-mediated tissue damage or aid in clearing MPO during inflammation resolution.
