Functional alterations of macrophages in autoimmune MRL-lpr/lpr mice.
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.
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D001323:Autoantibodies / Q000276:immunology; D002448:Cell Adhesion; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000276:immunology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology*; D010529:Peritoneal Cavity / Q000166:cytology; D010587:Phagocytosis
D001323:Autoantibodies; D008070:Lipopolysaccharides; D007371:Interferon-gamma; D004247:DNA; D006861:Hydrogen Peroxide