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Correlation of immunogenicity and production of ornithine by peritoneal macrophages
Abstract:
The release of ornithine by macrophages and its correlation with their immunogenicity after treatment with various macrophage-stimulating substances were analyzed. Pristane-elicited peritoneal macrophages (PM) were found to express strong arginase activity and to release L-ornithine into the extracellular space. This activity is strongly reduced within 3 hr after treatment with tetradecanoylphorbol acetate (TPA) but not with lipopolysaccharide (LPS). Resident PM usually express little arginase activity, but this activity is markedly augmented within 24 or 48 hr after treatment with LPS. The release of ornithine by peritoneal cells (PC) (60 to 90% macrophages) was found to be correlated with their immunogenicity as determined by the in vivo immunization for a subsequent in vitro secondary cytotoxic response against minor H antigens. The immunogenicity of pristane-elicited PC is markedly stronger than that of resident PC or TPA-treated, pristane-elicited PC. Moreover, the immunogenicity of the resident PC and TPA-treated elicited PC is substantially augmented by the simultaneous injection of ornithine, whereas the immunogenicity of the untreated elicited PC is not further augmented by exogenous ornithine, indicating that the endogenous production of ornithine by the stimulating cells had a strong influence on the resulting immune response. Injection of glutathione into pristane-treated mice also reduces the ornithine production and immunogenicity of the resulting peritoneal exudate cells. The immunogenicity in this case is at least partly reconstituted by application of exogenous ornithine. Our experiments revealed no correlation between the production of ornithine and prostaglandin E2. Prostaglandin E2 production of resident and pristane-elicited PC is not markedly different and is in either case strongly augmented by TPA. Elicited or resident PM which have been incubated for several days in culture release practically no ornithine; but ornithine production can be induced again by incubation for 24 hr with LPS and to some extent also with interferon-gamma.
Insights
Macrophages release L-ornithine, influencing their immune response. This ornithine production is linked to immunogenicity, with its levels affected by various treatments and substances like TPA and LPS.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Macrophages play a crucial role in immune responses.
- Ornithine metabolism is implicated in cellular functions.
- Macrophage activation influences their immunogenicity.
Purpose of the Study:
- To analyze L-ornithine release by macrophages.
- To investigate the correlation between ornithine release and macrophage immunogenicity.
- To determine the effects of various stimulating substances on macrophage arginase activity and ornithine production.
Main Methods:
- Analysis of arginase activity in peritoneal macrophages (PM).
- Measurement of L-ornithine release by peritoneal cells (PC).
- Assessment of immunogenicity using in vivo immunization and in vitro cytotoxic response assays.
- Treatment of mice and cells with substances like pristane, TPA, LPS, glutathione, and interferon-gamma.
Main Results:
- Pristane-elicited PM exhibit high arginase activity and L-ornithine release, which is reduced by TPA but not LPS.
- LPS treatment augments arginase activity in resident PM.
- Ornithine release by PC correlates positively with their immunogenicity.
- Exogenous ornithine enhances the immunogenicity of resident and TPA-treated elicited PC, but not untreated elicited PC.
- Glutathione reduces ornithine production and immunogenicity in pristane-treated mice.
- No correlation was found between ornithine and prostaglandin E2 production.
- LPS and interferon-gamma can re-induce ornithine production in cultured PM.
Conclusions:
- Endogenous ornithine production by macrophages significantly influences their immunogenicity.
- Macrophage activation state and treatment dictate ornithine release and subsequent immune response.
- Ornithine metabolism is a key factor in modulating macrophage-based immunity.