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Loss of lysosomal neutral proteinase from leucocytes induced by the action of multiple sclerosis-specific brain
Abstract:
Lysosomal neutral proteinase levels were assayed in leukocytes of patients with other neurological diseases before and after the reaction with MS-specific brain antigens (MSG2). The lysosomal neutral proteinase activity of MS leucocytes was found to be higher than in the two other groups under investigation. To assay the effect of MSG2, 1 x 10(6) leucocytes were incubated with 500 ng of protein MSG2 and with 500 ng of protein of a corresponding fraction from control brain (KG2). Intracellular levels of lysosomal neutral proteinase in leucocytes of all the subjects studied were found to be lowered by the action of both MSG2 and KG2. However, loss of intracellular neutral proteinase induced by the action of MSG2 on all leucocytes was significantly higher than that by KG2 (P less than 0 . 0025). It is suggested that macrophages (monocytes) were stimulated to increased lysosomal enzyme activity, initiated by stimulation of T lymphocytes caused by MS-specific brain antigens.
Insights
Multiple Sclerosis (MS) patients
Area of Science:
- Neuroimmunology
- Biochemistry
Background:
- Lysosomal neutral proteinases play a role in immune responses.
- Elevated proteinase activity may be implicated in Multiple Sclerosis (MS) pathogenesis.
Purpose of the Study:
- To investigate lysosomal neutral proteinase activity in leukocytes of MS patients.
- To determine the effect of MS-specific brain antigens on proteinase levels.
Main Methods:
- Leukocytes from MS patients and controls were incubated with MS-specific brain antigens (MSG2) or control brain fractions (KG2).
- Intracellular levels of lysosomal neutral proteinase were measured before and after antigen exposure.
Main Results:
- Leukocytes from MS patients exhibited higher basal lysosomal neutral proteinase activity compared to controls.
- Both MSG2 and KG2 reduced intracellular proteinase levels.
- MSG2 induced a significantly greater loss of proteinase than KG2.
Conclusions:
- MS-specific brain antigens may stimulate T lymphocytes, leading to increased macrophage/monocyte activity.
- This stimulation results in enhanced lysosomal enzyme activity, potentially contributing to MS.
- Further research into MS-specific antigens and immune cell responses is warranted.