Prolonged circulation of immune complexes due to various altered immune functions contributes to nephritis in MRL/lpr mice.
To gain some insight into the pathogenesis of proliferative lupus nephritis in MRL/lpr mice we investigated the kinetics of removal of immune complexes from the circulation, the carrier state of blood cells, the uptake of complexes by the mononuclear phagocyte system, and the localization of complexes in kidneys. In nephritic MRL/lpr mice challenged with a subsaturating dose of radiolabelled complexes (2.5 mg bovine serum albumin-anti-bovine serum albumin) liver uptake was profoundly decreased, removal of circulating complexes was delayed, and 12-h kidney localization of complexes was enhanced 7.3-fold, in comparison to control mice. The findings were not encumbered by differences in complement concentration and most likely are attributable to various altered immune functions: spontaneous polyclonal activation of B cells, enhanced production of endogenous immune complexes, delayed removal of complexes from the circulation, and decreased uptake of complexes by the mononuclear phagocyte system. In concert, such altered functions contribute to prolonged circulation of complexes to result in their enhanced deposition in the microcirculation.
Granholm
N A
NA
Department of Pathology, Rhode Island Hospital, Providence 02903.
Cavallo
T
T
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008181:Lupus Nephritis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010586:Phagocytes / Q000378:metabolism
D000936:Antigen-Antibody Complex