Reduced cell yields of mouse cell line cultures after exposure to homogenates of multiple sclerosis tissues
Abstract:
The total cell yields in cultures of a mouse cell line termed "PAM" were reduced markedly after exposure to multiple sclerosis (MS) homogenates. The reductions were noted as early as the second subcultivation. The effect was produced by eight of eight MS brain homogenates and three of three MS spleen homogenates; the samples were from 10 MS cases. The reduction in total cell yields (compared to medium-treated cultures) was not observed after exposure to homogenates, six brain and two spleen, from eight non-MS cases. The effect was produced by the 50-nm filtrate of a pool of MS brain homogenates. Five of the MS-inoculated cultures were maintained for 18 subcultivations, and the reduction in total cell yields persisted throughout the series. The capacity to induce the reduction in cell yields was present in cell-free lysates from five of five MS cultures at passage 18, as was the capacity to cause a decrease in the polymorphonuclear neutrophils in the peripheral blood of mice. Calculation of the dilution effect (at least 10(18)-fold) that had occurred by the end of the passage series proved that the factor(s) causing the cell change in culture and the polymorphonuclear neutrophil change in mice had replicated in PAM cells.
Insights
Multiple sclerosis (MS) homogenates significantly reduced mouse cell yields in cultures. This effect persisted through multiple subcultivations, indicating a replicating factor in MS samples.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system.
- The etiology of MS remains incompletely understood, with potential roles for environmental factors.
- Investigating cellular responses to MS-associated materials can provide insights into disease mechanisms.
Purpose of the Study:
- To investigate the effect of multiple sclerosis (MS) homogenates on mouse cell line growth.
- To determine if the causative factor in MS homogenates replicates within cell cultures.
- To assess the correlation between cellular changes and in vivo effects on mouse immune cells.
Main Methods:
- Exposure of a mouse cell line (PAM) to homogenates from MS and non-MS brain and spleen tissues.
- Monitoring total cell yields across multiple subcultivations.
- Filtration of MS homogenates to isolate potential causative agents.
- Assessing cell-free lysates for their capacity to induce cellular changes and affect peripheral blood polymorphonuclear neutrophils in mice.
Main Results:
- MS homogenates markedly reduced total cell yields in PAM cultures, starting from the second subcultivation.
- This reduction was observed with homogenates from 10 MS cases but not from 8 non-MS cases.
- The effect persisted for 18 subcultivations and was attributed to a replicating factor present in MS samples, also affecting mouse neutrophils.
Conclusions:
- A factor present in multiple sclerosis (MS) homogenates significantly inhibits mouse cell line growth.
- This factor appears to replicate within the cultured cells, suggesting an infectious or self-propagating mechanism.
- The findings suggest a potential role for a transmissible agent or a novel biological mechanism in MS pathogenesis.
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