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Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
Nav1.5 sodium channels in macrophages in multiple sclerosis lesions
Joel A Black1, Jia Newcombe, Stephen G Waxman
1Department of Neurology and Paralyzed Veterans of America Center for Neuroscience and Regeneration Research, Yale University School of Medicine, USA. joel.black@yale.edu
Background:
Macrophages are dynamic participants in destruction of white matter in active multiple sclerosis (MS) plaques. Regulation of phagocytosis and myelin degradation along endosomal pathways in macrophages is highly-orchestrated and critically-dependent upon acidification of endosomal lumena. Evidence from in vitro studies with macrophages and THP-1 cells suggests that sodium channel Nav1.5 is present in the limiting membrane of maturing endosomes where it plays a prominent role in the accumulation of protons. However, a contribution of the Nav1.5 channel to macrophage-mediated events in vivo has not been demonstrated.
Method:
We examined macrophages within active MS lesions by immunohistochemistry to determine whether Nav1.5 is expressed in these cells in situ and, if expressed, whether it is localized to specific compartments along the endocytic pathway.
Results:
Our results demonstrate that Nav1.5 is expressed within macrophages in active MS lesions, and that it is preferentially expressed in late endosomes and phagolysosomes (Rab7(+), LAMP-1(+)), and sparsely expressed in early (EEA-1(+)) endosomes. Triple-immunolabeling studies showed localization of Nav1.5 within Rab7(+) endosomes containing proteolipid protein, a myelin marker, in macrophages within active MS plaques.
Conclusions:
These observations support the suggestion that Nav1.5 contributes to the phagocytic pathway of myelin degradation in macrophages in vivo within MS lesions.
Insights
Sodium channel Nav1.5 is found in macrophages within active multiple sclerosis (MS) lesions. This channel is crucial for myelin degradation in macrophages during MS plaque destruction.
Area of Science:
- Neuroimmunology
- Cell Biology
- Molecular Medicine
Background:
- Macrophages are key in white matter destruction in active multiple sclerosis (MS) plaques.
- Endosomal acidification regulates phagocytosis and myelin degradation in macrophages.
- In vitro studies suggest Nav1.5 channels aid proton accumulation in macrophage endosomes.
Purpose of the Study:
- To investigate Nav1.5 expression in macrophages within active MS lesions.
- To determine the localization of Nav1.5 within the endocytic pathway of these cells in vivo.
Main Methods:
- Immunohistochemistry was used to examine macrophages in active MS lesions.
- Cells were analyzed for Nav1.5 expression and localization within endosomal compartments.
Main Results:
- Nav1.5 is expressed in macrophages within active MS lesions.
- Preferential localization of Nav1.5 was observed in late endosomes and phagolysosomes (Rab7+, LAMP-1+).
- Nav1.5 was found in endosomes containing proteolipid protein, a myelin marker.
Conclusions:
- Nav1.5 is present in macrophages in active MS lesions.
- The channel is localized to compartments involved in myelin degradation.
- These findings support a role for Nav1.5 in the in vivo phagocytic pathway of myelin breakdown in MS.
