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Published on: May 31, 2018
The release of cytokines by macrophages is not affected by myelin ingestion
J E Glim1, E J F Vereyken, D A M Heijnen
1Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam.
Abstract:
Macrophages play an important role in demyelination in multiple sclerosis (MS). Activated macrophages ingest myelin particles, thereby acquiring a foamy appearance. Foamy macrophages in MS lesions were described as being anti-inflammatory. Therefore, these cells might play a role in modulating the inflammatory state of an active lesion. Here, we investigated the mechanism by which myelin uptake leads to skewing of macrophages toward an anti-inflammatory phenotype. Macrophages were incubated with myelin, leading to the development of foamy macrophages. Afterwards, the cells were stimulated with the TLR-4 ligand lipopolysaccharide (LPS), and cytokine production was determined. Interestingly, foamy macrophages appeared to have a reduced cytokine secretion and were LPS insensitive only when generated with one of the myelin preparations. The factor responsible for the different outcomes between different myelin batches turned out to be LPS. We demonstrated that LPS contamination induced insensitivity to LPS in foamy macrophages. On the contrary, foamy macrophages generated in the presence of LPS-free myelin were able to secrete cytokines upon activation. To conclude, myelin-laden macrophages were not LPS insensitive, indicating that they had not acquired an anti-inflammatory phenotype.
Insights
Foamy macrophages in multiple sclerosis (MS) are not inherently anti-inflammatory. Myelin uptake does not induce an anti-inflammatory phenotype; rather, lipopolysaccharide (LPS) contamination in myelin causes LPS insensitivity in these cells.
Area of Science:
- Neuroimmunology
- Cellular Biology
Background:
- Macrophages are crucial in multiple sclerosis (MS) pathogenesis, particularly in demyelination.
- Foamy macrophages, resulting from myelin ingestion, have been suggested to possess anti-inflammatory properties in MS lesions.
Purpose of the Study:
- To investigate the mechanism by which myelin uptake influences macrophage phenotype.
- To determine if myelin uptake induces an anti-inflammatory state in macrophages.
Main Methods:
- Macrophages were incubated with myelin to induce a foamy appearance.
- Foamy macrophages were subsequently stimulated with lipopolysaccharide (LPS).
- Cytokine production was measured to assess macrophage inflammatory response.
Main Results:
- Foamy macrophages exhibited reduced cytokine secretion and LPS insensitivity, but only when myelin preparations contained LPS.
- LPS contamination in myelin was identified as the factor causing LPS insensitivity.
- Foamy macrophages generated with LPS-free myelin remained responsive to LPS stimulation and secreted cytokines.
Conclusions:
- Myelin-laden macrophages do not acquire an inherent anti-inflammatory phenotype.
- The observed LPS insensitivity in foamy macrophages is attributable to LPS contamination, not myelin uptake itself.
- This finding challenges the notion of foamy macrophages as solely anti-inflammatory in MS lesions.
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