Monocyte and polymorphonuclear leukocyte toxic oxygen metabolite production in multiple sclerosis
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M Fisher1, P H Levine, B H Weiner
1Department of Neurology, Worcester Memorial Hospital, Massachusetts.
Abstract:
Lipid-laden macrophages, which are predominantly derived from blood monocytes, are present at sites of active multiple sclerosis demyelination and are assumed to be involved in the demyelinating process. These inflammatory cells produce a variety of toxic oxygen metabolites which can mediate host tissue destruction. We measured production of two oxygen metabolites by monocytes and polymorphonuclear leukocytes in MS patients and controls. Stimulated monocytes produced significantly more hydrogen peroxide, superoxide, and chemiluminescence in the MS group than controls. The polymorphonuclear leukocyte, an inflammatory cell that appears to contribute little to MS demyelination, did not demonstrate increased production of toxic oxygen metabolites in the MS patients as compared to controls. These results suggest that blood monocytes in MS patients are primed to produce increased amounts of cytotoxic oxygen metabolites when exposed to inflammatory stimuli.
Insights
Multiple sclerosis patients have blood monocytes that produce more toxic oxygen metabolites. These inflammatory cells may contribute to demyelination and tissue damage in multiple sclerosis.
Area of Science:
- Neuroimmunology
- Cellular immunology
Background:
- Lipid-laden macrophages are found at sites of demyelination in multiple sclerosis (MS).
- These macrophages, derived from blood monocytes, are implicated in the demyelinating process.
- Inflammatory cells can produce toxic oxygen metabolites, potentially causing tissue damage.
Purpose of the Study:
- To investigate the production of oxygen metabolites by monocytes and polymorphonuclear leukocytes in multiple sclerosis patients.
- To determine if monocytes from MS patients exhibit heightened reactivity to inflammatory stimuli.
Main Methods:
- Monocytes and polymorphonuclear leukocytes were isolated from multiple sclerosis patients and healthy controls.
- Production of hydrogen peroxide and superoxide was measured following stimulation.
- Chemiluminescence was assessed as an indicator of reactive oxygen species generation.
Main Results:
- Stimulated monocytes from MS patients produced significantly higher levels of hydrogen peroxide and superoxide compared to controls.
- Increased chemiluminescence was observed in stimulated monocytes from the MS group.
- Polymorphonuclear leukocytes did not show increased oxygen metabolite production in MS patients.
Conclusions:
- Blood monocytes in multiple sclerosis patients are primed to produce elevated levels of cytotoxic oxygen metabolites.
- This heightened monocyte reactivity may contribute to demyelination and tissue injury in multiple sclerosis.
- Polymorphonuclear leukocytes appear to play a minimal role in MS-associated oxidative damage.