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L-fucosidase treatment blocks myelin phagocytosis by macrophages in vitro
1Department of Neuropathology, University of Göttingen, F.R.G.
Abstract:
Myelin phagocytosis in nerves undergoing Wallerian degeneration has been shown to depend on their invasion by non-resident, hematogenous macrophages. This process can be studied in vitro using organ cultures of peripheral nerves exposed to cultured peritoneal macrophages. The present report concerns the role of cell surface carbohydrates in the invasion of degenerating nerves and in the recognition and ingestion of myelin by the phagocytic cells. Additional experiments explored the effect of pH, calcium and cytochalasin D on myelin phagocytosis. Organ cultures with peritoneal macrophages were treated with 14 simple or complex sugars or with eight sugar-splitting enzymes. Macrophage invasion was diminished by many simple or complex sugars, but exposure to sugars had no effect on the recognition or ingestion of myelin by the invading macrophages. Macrophage invasion was abolished upon treatment with beta-mannosidase. Exposure to L-fucosidase abolished the myelin phagocytic capacity of invading macrophages completely without affecting their capacity to ingest carbon or latex particles. The results indicate that the phagocytosis of myelin by macrophages is an L-fucosidase-sensitive process, probably by interaction with their complement receptor type C3.
Insights
Macrophage invasion into degenerating nerves is carbohydrate-dependent. L-fucosidase treatment abolished myelin phagocytosis, indicating its crucial role in this process.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Wallerian degeneration involves myelin breakdown in nerves.
- Hematogenous macrophages are crucial for clearing myelin debris.
- Cell surface carbohydrates play roles in cell-cell interactions.
Purpose of the Study:
- To investigate the role of cell surface carbohydrates in macrophage invasion of degenerating nerves.
- To determine the effect of specific sugars and enzymes on myelin phagocytosis.
- To explore the influence of pH, calcium, and cytochalasin D on this process.
Main Methods:
- Organ cultures of peripheral nerves were exposed to peritoneal macrophages.
- Cultures were treated with various sugars and sugar-splitting enzymes.
- Myelin phagocytosis was assessed after enzymatic or chemical treatments.
Main Results:
- Macrophage invasion was reduced by several sugars but not their recognition/ingestion of myelin.
- Beta-mannosidase abolished macrophage invasion.
- L-fucosidase completely inhibited myelin phagocytosis without affecting other particle ingestion.
Conclusions:
- Myelin phagocytosis by macrophages is sensitive to L-fucosidase.
- This process likely involves interactions with the complement receptor type C3.
- Cell surface carbohydrates are critical for macrophage-mediated myelin clearance during nerve degeneration.
