Abnormal binding of soluble IgG immune complexes to hepatic nonparenchymal cells of autoimmune mice.
Abnormal binding of soluble IgG immune complexes to hepatic nonparenchymal cells of autoimmune mice.
复制标题
可溶性 IgG 免疫复合物与自身免疫小鼠肝非实质细胞的异常结合。
作者：
D. Magilavy;T. Hundley;A. Steinberg;D. Finbloom
由于肝脏是负责去除可溶性免疫复合物 (IC) 的主要器官，因此研究了预制模型 IC 与悬浮液中未刺激的小鼠肝脏非实质细胞 (NPC) 的表面结合特性。通过用胶原酶灌注门静脉，然后用甲曲酰胺梯度从肝细胞中分离 NPC，分离不同年龄的非自身免疫性 C3H/FeJ、C3H/HeJ、A/J、DBA/2 和自身免疫性 NZB/W F1 和 MRL/lpr 雌性小鼠的 NPC。所有小鼠品系中 35% 的 NPC 呈非特异性酯酶阳性并被吞噬乳胶珠。通过凝胶过滤分离放射性标记的小鼠 IgG 抗 DNP 共价交联稳定 IC，并在各种条件下与 NPC 结合。自身免疫小鼠品系和非自身免疫小鼠品系之间每个细胞结合的 IC 最大数量存在显着差异：非自身免疫品系小鼠为 3.3 至 4.0 X 10(5)，而自身免疫品系小鼠在 1 至 6 个月时每个细胞结合的 IC 分子为 0.3 至 1.4 X 10(5)。通过斯卡查德图分析 (3.5 至 5.0 X 10(8) M-1) 和通过表面结合 IC 与过量热聚集丙种球蛋白解离确定的结合可逆性速率 (T 1/2:1.5 至 2 分钟) 发现，Ka 存在不显着差异。这些数据表明，在未受刺激的 NZB/W F1 和 MRL/lpr 雌性小鼠的 NPC 中，IC 的可用结合位点数量在其整个生命周期中减少。尽管这些发现与 NPC 与天然 IC 的结合位点饱和一致，但在 1 个月大的自身免疫小鼠（没有可检测到的自身抗体）中发现的异常表明 FC 受体表达的主要缺陷或 NPC 激活状态的改变可能导致疾病过程。
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.