Abnormal binding of soluble IgG immune complexes to hepatic nonparenchymal cells of autoimmune mice.
Because the liver is the major organ responsible for removal of soluble immune complexes (IC), the surface binding characteristics of preformed model IC to unstimulated mouse liver nonparenchymal cells (NPC) in suspension were studied. NPC of non-autoimmune C3H/FeJ, C3H/HeJ, A/J, DBA/2 and the autoimmune NZB/W F1 and MRL/lpr female mice of various ages were isolated by perfusion of the portal vein with collagenase followed by separation of NPC from hepatocytes with a metrizamide gradient. Thirty-five percent of NPC of all mouse strains were nonspecific esterase-positive and phagocytosed latex beads. Radiolabeled mouse IgG anti-DNP covalently cross-linked stable IC were separated by gel filtration and bound to NPC under various conditions. Marked differences were noted in maximal number of IC bound per cell between the autoimmune and non-autoimmune mouse strains: 3.3 to 4.0 X 10(5) in the non-autoimmune strains vs 0.3 to 1.4 X 10(5) molecules of IC bound per cell in the autoimmune strains at 1 to 6 mo. Insignificant differences were noted in Ka by Scatchard plot analysis (3.5 to 5.0 X 10(8) M-1) and rate of reversibility of binding as determined by dissociation of surface-bound IC with an excess of heat-aggregated gamma-globulin (T 1/2:1.5 to 2 min). These data demonstrate a decreased number of available binding sites for IC in unstimulated NPC from NZB/W F1 and MRL/lpr female mice throughout their life spans. Although the findings are consistent with saturation of binding sites of the NPC with native IC, the abnormality found in the 1-mo-old autoimmune mice (who do not have detectable autoantibodies) suggests a primary defect in FC receptor expression or an altered state of activation of NPC that may contribute to the disease process.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D001666:Binding Sites, Antibody; D002470:Cell Survival; D005260:Female; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism; D011961:Receptors, Fc / Q000032:analysis; D017452:Receptors, IgG
D000936:Antigen-Antibody Complex; D011961:Receptors, Fc; D017452:Receptors, IgG