モデル免疫複合体による実験的糸球体腎炎
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概要
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A new bivalent hapten of p-aminohippuric acid (PAH) , a known antigen determinant, was synthesized using adipoyl chloride. Between this hapten, 4,4'-adipoyldiiminobis (hippuric acid) and anti-PAH antibody a minimum-sized immune complex comprising two molecules of IgG was formed in vitro, which is of no exposure of antigen molecule and stable thermodynamically. The dimeric IgG-complex (Dimer IC) has no activation to complement function and phagocytic response of PMN, different from the larger complex (Large IC) formed between anti-PAH antibody and PAH・ovalbumin, however, it induced a critical proliferative glomerulonephritis accompanying proteinuria (50-150mg/day) in high frequency when intravenously administered daily to 9 week-aged mice for consecutive 5 days after the intraperitoneal pretreatment with Large IC and similarly to the older mice, 19 week-aged, without the pretreatment, whereas Large IC alone caused no glomerular abnormality. The histopathological renal examination revealed serious changes such as the enlargement of mesangial matrix and segmental necrosis of glomerular tufts with capillary thrombi in the diseased mice. Dimer IC, unlike Large IC, seems to be able to pass through the reticuloendothelial clearance system easily to deposit on the glomeruli. The possibly abundant deposits of Dimer IC supposedly take a special plane configuration capable of complement fixation leading to the outbreak of glomerular inflammation. The present study will evidently suggest a contributing role of the circulating smaller IC, dimer or trimer, to the onset of glomerulonephritis in human.
- 神戸大学の論文