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Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation
Published on: May 16, 2016
Effect of endotoxin on cells and on their response to infection by polioviruses
Abstract:
Murphy, W. H. (The University of Michigan, Ann Arbor) and C. Wisner. Effect of endotoxin on cells and on their response to infection by polioviruses. J. Bacteriol. 83:649-662. 1962.-The effect of lipopolysaccharide on HeLa-S3, HeLa-Gey, Chang-liver, Maben, and L strain mouse fibroblasts was studied. The liminal dose of endotoxin for the human epithelial cell strains was approximately 250 mug/ml, and their order of sensitivity to endotoxin was: Chang-liver, HeLa-Gey, HeLa-S3, and Maben, the latter being the most resistant. Endotoxin at concentrations exceeding 100 mug/ml was cytotoxic to the L strain of mouse fibroblasts and caused them to markedly agglutinate. Cytotoxic response of cells to endotoxin was not characterized by cell lysis, but by distinctive nuclear changes. In an attempt to demonstrate the metabolic induction of the latent infection of cell cultures by a noncytopathic variant of poliovirus, endotoxin was added at maximal subliminal concentration to cell cultures totally, partially, or fully susceptible to virus. Endotoxin caused a slight but consistent accelerative cytopathic response of cells to infection by cytopathic poliovirus, but failed to induce cytopathic response to infection by submoderate (noncytopathic) poliovirus. Although endotoxin slightly suppressed yields of poliovirus from cells, it did not affect the plating efficiency of virus on cell monolayers.
Insights
Lipopolysaccharide (endotoxin) affects cell sensitivity and response to poliovirus infections. While it accelerates cytopathic effects with some poliovirus strains, it does not induce infections in noncytopathic poliovirus strains.
Area of Science:
- Microbiology
- Cell Biology
- Virology
Background:
- Lipopolysaccharide (endotoxin) is a component of Gram-negative bacteria.
- Endotoxin can modulate cellular responses and immune functions.
- The interaction between endotoxin and viral infections in cell cultures requires further elucidation.
Purpose of the Study:
- To investigate the cytotoxic effects of endotoxin on various human and mouse cell lines.
- To determine the impact of endotoxin on cellular susceptibility and response to poliovirus infection.
- To explore if endotoxin can induce latent poliovirus infections.
Main Methods:
- Exposure of HeLa-S3, HeLa-Gey, Chang-liver, Maben, and L strain mouse fibroblasts to varying concentrations of endotoxin.
- Assessment of cell viability, agglutination, and nuclear changes following endotoxin treatment.
- Infection of endotoxin-treated cell cultures with cytopathic and noncytopathic poliovirus strains.
- Quantification of poliovirus yields and plating efficiency.
Main Results:
- Differential sensitivity of cell strains to endotoxin, with Chang-liver cells being most sensitive and Maben cells most resistant.
- Cytotoxic effects on L strain mouse fibroblasts at concentrations above 100 mug/ml, characterized by nuclear changes, not lysis.
- Endotoxin slightly accelerated cytopathic effects of cytopathic poliovirus but did not induce responses to noncytopathic poliovirus.
- Endotoxin marginally reduced poliovirus yields but did not alter virus plating efficiency.
Conclusions:
- Endotoxin exhibits dose-dependent cytotoxic and agglutinative effects on specific cell lines.
- Endotoxin can modulate the cellular response to certain viral infections but does not induce latent viral activity.
- The findings highlight the complex interplay between bacterial endotoxins and viral pathogenesis in cell culture models.
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