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Scrapie-induced changes in the percentage of polymorphonuclear neutrophils in mouse peripheral blood
Abstract:
A decrease in the percentage of polymorphonuclear neutrophils (PMN) in the peripheral blood of mice appeared 3 days after intracerebral (IC) inoculation with scrapie mouse brain homogenate. Mice inoculated IC with normal mouse brain had PMN percentages similar to those found for uninoculated mice. This difference between normal and scrapie-inoculated mice continued throughout the preclinical phase of the disease. In the clinical phase of the disease, the percentage of PMN was either higher or lower than that found in normals. The factor causing the decrease in PMN percentages was found in the filtrates from 220-, 100-, and 50-nm filters, but not in the filtrates from a 25-nm filter. Sodium periodate treatment of the scrapie brain samples eliminated their ability to cause the decrease in PMN percentages, whereas sodium iodate had no effect. In addition to two genetically different scrapie mouse brain isolates, homogenates of mouse spleen, sheep brain, and sheep spleen from scrapie-affected animals caused a decrease in percent PMN, whereas the corresponding normal tissue homogenates did not.
Insights
Scrapie infection in mice causes a significant decrease in polymorphonuclear neutrophils (PMN) during the preclinical phase. This effect is linked to a transmissible factor in affected brain and spleen tissues.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Scrapie is a transmissible spongiform encephalopathy affecting the central nervous system.
- Changes in peripheral blood cell populations can indicate underlying disease processes.
Purpose of the Study:
- To investigate the effect of scrapie infection on peripheral polymorphonuclear neutrophils (PMN) in mice.
- To identify characteristics of the scrapie-associated factor influencing PMN levels.
Main Methods:
- Intracerebral inoculation of mice with scrapie or normal brain homogenates.
- Filtration of brain homogenates to isolate the causative agent.
- Chemical treatment (sodium periodate, sodium iodate) to characterize the factor.
- Analysis of peripheral blood PMN percentages over time.
Main Results:
- A decrease in peripheral blood PMN percentage was observed starting 3 days post-intracerebral inoculation with scrapie.
- This PMN reduction persisted throughout the preclinical phase.
- The factor causing PMN decrease was retained by 50-nm filters but not 25-nm filters.
- Sodium periodate treatment abolished the PMN-decreasing activity of scrapie samples.
- Scrapie-affected brain and spleen homogenates from mice and sheep induced similar PMN reductions.
Conclusions:
- Scrapie infection induces a specific, transient decrease in peripheral PMN percentages during its preclinical phase.
- The responsible agent is a large molecule, likely proteinaceous, sensitive to periodate oxidation.
- This finding suggests a potential biomarker for early scrapie detection.