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Functional alterations of macrophages in autoimmune MRL-lpr/lpr mice
Abstract:
To assess the role of macrophages (MAC) in the pathogenesis of systemic lupus erythematosus, we investigated functional aspects of peritoneal MAC obtained from autoimmune MRL/MpJ-lpr/lpr (MRL-lpr) mice. MRL-lpr and control C3H/HeN MAC were obtained from untreated mice or mice injected i.p. with 1 ml of 10% sterile peptone 3 days before cell harvest. MRL-lpr mice had significantly more peritoneal cells (MAC and lymphocytes) than did control mice. In endotoxin-free conditions, MRL-lpr MAC were similar to C3H/HeN MAC in their baseline, and IFN-gamma and/or LPS enhanced cytolysis of 3T12 fibrosarcoma tumor cells. Compared with C3H/HeN MAC, MRL-lpr MAC had a significant increase in antibody-dependent cellular cytotoxicity activity against sheep erythrocytes. This enhanced activity was not accompanied by a similar increase in adherence and/or phagocytosis of the same targets. Finally, in response to phorbol myristate acetate stimulation, both resident and peptone-induced MAC from MRL-lpr mice produced significantly more hydrogen peroxide than did those from control mice. These results indicate that MAC from MRL-lpr mice display features of selective "activation", and suggest that MAC or their products may play a role in the pathogenesis of inflammatory disorders seen in autoimmune diseases.
Insights
Macrophages (MAC) from autoimmune MRL-lpr mice show selective activation, with enhanced cytotoxic activity and hydrogen peroxide production. These findings suggest a role for MAC in the inflammatory pathology of systemic lupus erythematosus.
Area of Science:
- Immunology
- Pathogenesis of autoimmune diseases
Background:
- Systemic lupus erythematosus (SLE) is a chronic autoimmune disease.
- Macrophages (MAC) are key immune cells implicated in autoimmune conditions.
Purpose of the Study:
- To investigate the functional characteristics of peritoneal macrophages from autoimmune MRL/MpJ-lpr/lpr (MRL-lpr) mice.
- To assess the potential role of these macrophages in the pathogenesis of SLE.
Main Methods:
- Peritoneal macrophages were isolated from MRL-lpr mice and control C3H/HeN mice.
- Functional assays included cytolysis of tumor cells, antibody-dependent cellular cytotoxicity (ADCC) against sheep erythrocytes, and hydrogen peroxide production.
- Cells were analyzed under baseline, IFN-gamma, LPS, and phorbol myristate acetate (PMA) stimulated conditions.
Main Results:
- MRL-lpr mice exhibited increased peritoneal cell counts (macrophages and lymphocytes).
- MRL-lpr macrophages showed enhanced antibody-dependent cellular cytotoxicity (ADCC) activity compared to controls.
- Macrophages from MRL-lpr mice produced significantly higher levels of hydrogen peroxide upon PMA stimulation.
Conclusions:
- Macrophages from MRL-lpr mice display features of selective activation.
- These activated macrophages may contribute to the inflammatory pathology observed in autoimmune diseases like SLE.