Superoxide and hydrogen peroxide production by macrophages of New Zealand black mice
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S H Khan1, I Emerit, J Feingold
1Institut biomedical des Cordeliers, CNRS, Paris.
Abstract:
Resident peritoneal macrophages from New Zealand Black (NZB) mice release O2- and H2O2 after adherence to a plastic surface without any chemical or particulate stimulant. This phenomenon is age dependent and more pronounced in animals with sever autoimmune disease. Significant differences were observed between the high and low breakage NZB sublines (HB and LB), which were previously developed by selective matings on the basis of chromosome breakage rates. The LB subline differs significantly from the HB subline with respect to autoimmune hemolytic anemia and tumor incidence. When the macrophages were stimulated with the tumor promoter TPA, the number of "responders" was higher in the HB than in the LB subline and correlated with the degree of splenomegaly, that is, with the severity of the disease. A negative response to agonist stimulation and very low spontaneous production of active oxygen species was observed in NZW and Swiss mice, which is the normal finding for resident macrophages according to data from the literature. The increased superoxide and hydrogen peroxide production by macrophages of NZB mice is discussed with respect to autoimmune disease and cancer.
Insights
Resident macrophages from autoimmune-prone mice spontaneously produce reactive oxygen species, particularly superoxide and hydrogen peroxide. This production increases with age and disease severity, linking oxidative stress to autoimmune disease and cancer risk.
Area of Science:
- Immunology
- Cell Biology
- Genetics
Background:
- Resident peritoneal macrophages from New Zealand Black (NZB) mice exhibit spontaneous release of reactive oxygen species (ROS), including superoxide (O2-) and hydrogen peroxide (H2O2), upon adherence to surfaces.
- This phenomenon is age-dependent and exacerbated in NZB mice with severe autoimmune disease.
- Significant genetic variations exist between high (HB) and low (LB) breakage NZB sublines, impacting autoimmune hemolytic anemia and tumor incidence.
Purpose of the Study:
- To investigate the spontaneous and stimulated production of active oxygen species by macrophages in different NZB mouse sublines.
- To correlate macrophage ROS production with autoimmune disease severity and tumor incidence.
- To compare ROS production in NZB mice with control strains (NZW and Swiss mice).
Main Methods:
- Isolation and culture of resident peritoneal macrophages from NZB (HB and LB sublines), NZW, and Swiss mice.
- Measurement of spontaneous superoxide and hydrogen peroxide release.
- Stimulation of macrophages with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to assess "responder" cells.
- Correlation of ROS production with clinical parameters like splenomegaly and disease incidence.
Main Results:
- Macrophages from NZB mice, especially the HB subline, showed significantly higher spontaneous O2- and H2O2 production compared to NZW and Swiss mice.
- TPA stimulation resulted in a higher percentage of "responder" macrophages in the HB subline than in the LB subline.
- Increased ROS production in HB mice correlated with greater splenomegaly and more severe autoimmune disease.
- LB subline exhibited lower ROS production, reduced splenomegaly, and differed in autoimmune hemolytic anemia and tumor incidence compared to HB.
Conclusions:
- Increased spontaneous production of active oxygen species by macrophages is a characteristic feature of NZB mice, linked to their genetic predisposition to autoimmune disease.
- The level of ROS production correlates with disease severity and potentially influences autoimmune hemolytic anemia and tumor development.
- These findings suggest a role for oxidative stress in the pathogenesis of autoimmune disease and cancer in NZB mice.