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Nucleoside uptake in macrophages from various murine strains: a short-time and a two-step stimulation model
F Busolo1, L Conventi, M Grigolon
1Institute of Microbiology of Padua University, Faculty of Medicine, Italy.
Abstract:
Kinetics of [3H]-uridine uptake by murine peritoneal macrophages (pM phi) is early altered after exposure to a variety of stimuli. Alterations caused by Candida albicans, lipopolysaccharide (LPS) and recombinant interferon-gamma (rIFN-gamma) were similar in SAVO, C57BL/6, C3H/HeN and C3H/HeJ mice, and were not correlated with an activation process as shown by the amount of tumor necrosis factor-alpha (TNF-alpha) being released. Short-time exposure to all stimuli resulted in an increased nucleoside uptake by SAVO pM phi, suggesting that the tumoricidal function of this cell either depends from the type of stimulus or the time when the specific interaction with the cell receptor is taking place. Experiments with priming and triggering signals confirmed the above findings, indicating that the increase or the decrease of nucleoside uptake into the cell depends essentially on the chemical nature of the priming stimulus. The triggering stimulus, on the other hand, is only able to amplify the primary response.
Insights
Murine peritoneal macrophages (pM phi) show altered [3H]-uridine uptake after stimuli like Candida albicans and LPS. This nucleoside uptake change depends on the priming stimulus, not tumor necrosis factor-alpha release.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Kinetics of [3H]-uridine uptake by murine peritoneal macrophages (pM phi) are sensitive to various stimuli.
- Previous studies indicate alterations in nucleoside uptake following exposure to immune modulators.
Purpose of the Study:
- To investigate the effects of different stimuli on [3H]-uridine uptake in murine peritoneal macrophages.
- To determine the correlation between nucleoside uptake and tumor necrosis factor-alpha (TNF-alpha) release.
- To elucidate the role of priming and triggering signals in modulating macrophage nucleoside uptake.
Main Methods:
- Exposure of murine peritoneal macrophages from different mouse strains (SAVO, C57BL/6, C3H/HeN, C3H/HeJ) to stimuli including Candida albicans, lipopolysaccharide (LPS), and recombinant interferon-gamma (rIFN-gamma).
- Measurement of [3H]-uridine uptake kinetics.
- Quantification of tumor necrosis factor-alpha (TNF-alpha) release.
- Experimental design involving priming and triggering signals.
Main Results:
- Stimuli like Candida albicans, LPS, and rIFN-gamma induced similar alterations in [3H]-uridine uptake across different mouse strains.
- No correlation was observed between altered nucleoside uptake and TNF-alpha release.
- Short-term exposure to stimuli increased nucleoside uptake in SAVO pM phi.
- Priming stimulus determined the increase or decrease in nucleoside uptake, while the triggering stimulus amplified the primary response.
Conclusions:
- Macrophage nucleoside uptake kinetics are modulated by specific stimuli, independent of TNF-alpha production.
- The nature of the priming stimulus is critical in dictating the direction of nucleoside uptake changes.
- Triggering stimuli act to amplify the initial response mediated by the priming stimulus.