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Impaired apoptosis in mitogen-stimulated lymphocytes of patients with multiple sclerosis
B Macchi1, C Matteucci, U Nocentini
1Department of Neuroscience, University of Rome Tor Vergata, Italy.
Abstract:
We investigated the sensitivity to cell death of peripheral blood mononuclear cells (PBMCs) from patients with multiple sclerosis (MS). PBMCs from MS patients, following PHA stimulation, were less sensitive to cell death than those from healthy donors (mean +/- s.e.m., 22.5 +/- 1.9 in MS patients vs 36.5 +/- 2.8 in healthy controls; p = 0.0003). However, when Fas-agonist antibody was added, the increase in respect to apoptosis induced by mitogen alone was even higher in MS patients than in controls. In addition, PHA-activated PBMCs from MS patients showed higher surface expression of Fas than controls, while Bcl-2 expression was decreased. This finding raised the question of whether an impaired generation of apoptotic signals may be contributing to the immune component of MS.
Insights
Peripheral blood mononuclear cells (PBMCs) from multiple sclerosis (MS) patients show reduced sensitivity to cell death. This impaired apoptosis in MS PBMCs may contribute to the disease's immune component.
Area of Science:
- Immunology
- Cell Biology
- Neuroscience
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- The role of immune cell apoptosis in the pathogenesis of MS is not fully understood.
Purpose of the Study:
- To investigate the sensitivity to cell death of peripheral blood mononuclear cells (PBMCs) from MS patients.
- To explore the expression of apoptosis-related molecules, Fas and Bcl-2, in MS PBMCs.
Main Methods:
- PBMCs were isolated from MS patients and healthy donors.
- PBMCs were stimulated with phytohemagglutinin (PHA).
- Cell death sensitivity was assessed with and without Fas-agonist antibody; Fas and Bcl-2 expression was measured.
Main Results:
- PHA-stimulated PBMCs from MS patients exhibited significantly lower sensitivity to cell death compared to healthy controls.
- The addition of Fas-agonist antibody induced a greater increase in apoptosis in MS PBMCs than in controls.
- PHA-activated MS PBMCs showed increased surface Fas expression and decreased Bcl-2 expression.
Conclusions:
- Impaired apoptotic signaling in PBMCs may be a contributing factor to the immune dysregulation observed in multiple sclerosis.
- These findings suggest potential therapeutic targets related to apoptosis modulation in MS.