Defects in mononuclear phagocytic system (MPS) function in autoimmune MRL-lpr/lpr mice.

MRL-lpr/lpr mice develop an autoimmune disease similar to systemic lupus erythematosus. To determine whether mice of this strain develop defects in mononuclear phagocyte system (MPS) function similar to those observed in patients, the pattern of sequestration of labeled immune complexes was compared 90 min after infusion into MRL-lpr/lpr and into normal B6D2 mice. The amount of complexes persisting in the blood was increased, and the amount sequestered in the liver was significantly reduced in MRL-lpr/lpr mice in comparison to normal B6D2 controls. This defect was most evident in MRL-lpr/lpr mice of the ages of 25-26 weeks; mice of this age also demonstrated the greatest elevation of anti-DNA antibody levels. The role of the MRL strain background and of the lpr gene in determining this defect was investigated by analysis of MRL-+/-/+/- and of other lpr congenic strains (B6-lpr/lpr, AKR-lpr/lpr, and C3H-lpr/lpr). Both MRL-+/-/+/- and congenic lpr animals showed similar defects, although to a lesser degree than MRL-lpr/lpr mice. In contrast, MRL-lpr/lpr mice demonstrated normal clearance of heat-damaged red blood cells and heat-aggregated albumin. Thus MRL-lpr/lpr mice display a selective defect in MPS Fc receptor function and may provide a valuable model for elucidating the etiology and importance of MPS dysfunction in immune complex deposition disease.