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Strain-dependent cytotoxic effects of endotoxin for mouse peritoneal macrophages
Abstract:
The cytotoxic effects of bacterial lipopolysaccharides (LPS) on mouse leukocytes have been examined in vivo and in vitro. Intraperitoneal injection of LPS into C57BL/6 mice greatly reduced the recovery of mononuclear cells; LPS was cytotoxic for macrophages, but had a mitogenic effect on lymphocytes. Similar effects of LPS on peritoneal leukocytes were observed in vitro. When monolayers of adherent peritoneal cells were studied in vitro, cytotoxicity was also observed, suggesting that the effect of LPS on macrophages is direct and does not require participation by lymphocytes. Entirely different results were obtained when peritoneal macrophages from LPS-resistant C3H/HeJ mice were studied. LPS failed to activate lymphocytes and was not cytotoxic for macrophages in vitro or in vivo. The effect of LPS on polymorphonuclear leukocytes appeared to be the same in all mouse stains studied. Lipid A was shown to be the most biologically active portion of the LPS molecule. Whereas polysaccharide-deficient endotoxins extracted from rough mutants of Salmonella typhimurium were cytotoxic for macrophages in vitro, polysaccharides that lacked esterified fatty acids did not exhibit this activity. Since LPS may mediate its effects through affinity for mammalian cell membranes, the cellular unresponsiveness of C3H/H3J mice to LPS may reflect an inability of cells from LPS-resistant strains to interact with LPS at the membrane level.
Insights
Bacterial lipopolysaccharides (LPS) show cytotoxic effects on mouse macrophages but stimulate lymphocytes. LPS resistance in some mice strains suggests a cell membrane interaction mechanism.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Bacterial lipopolysaccharides (LPS) are potent immune modulators.
- LPS elicits diverse responses in host immune cells, including cytotoxicity and mitogenesis.
- Understanding LPS-host interactions is crucial for immunology and infectious disease research.
Purpose of the Study:
- To investigate the cytotoxic effects of bacterial lipopolysaccharides (LPS) on mouse leukocytes.
- To differentiate the effects of LPS on macrophages versus lymphocytes.
- To explore the mechanisms underlying LPS resistance in certain mouse strains.
Main Methods:
- In vivo and in vitro experiments using C57BL/6 and LPS-resistant C3H/HeJ mice.
- Analysis of peritoneal leukocytes, including macrophages and lymphocytes.
- Investigation of the role of Lipid A and polysaccharide components of LPS.
Main Results:
- LPS was cytotoxic to macrophages and mitogenic to lymphocytes in C57BL/6 mice.
- LPS did not affect macrophages or lymphocytes in LPS-resistant C3H/HeJ mice.
- Lipid A was identified as the most biologically active LPS component, with polysaccharide-deficient endotoxins retaining cytotoxicity.
Conclusions:
- The cytotoxic effect of LPS on macrophages is direct and does not require lymphocyte participation.
- Cellular unresponsiveness in LPS-resistant mice may stem from impaired cell membrane interaction with LPS.
- LPS-mediated effects are primarily associated with the Lipid A moiety and cell membrane interactions.