INDUCTION OF GLOMERULONEPHRITIS IN RATS WITH STAPHYLOCOCCAL PHOSPHATASE - NEW ASPECTS IN POSTINFECTIOUS ICGN

Staphylococcal neutral phosphatase (NPtase) is a highly cationic bacte rial surface bound protein. It has significant affinity for human and rat immunoglobulins in vitro and an electrostatic interaction may be i nvolved. Radioisotopic studies showed that NPtase had a high affinity for the polyanionic structures of the rat renal glomerulus. When the l eft kidneys of germ-free or naive (nonimmune) Wistar rats were perfuse d with 80 mu g of I-125 NPtase, 21 mu g of NPtase were found in the le ft kidneys and 11 mu g in the isolated glomeruli 15 minutes after perf usion. Deposits of autologous immunoglobulin and C3 were seen in the g lomeruli of rats immediately after perfusion with NPtase (15 min) and persisted throughout the 14-day observation period. Histologically, ne utrophil influx into the glomerulus was seen at 15 minutes and increas ed until three hours; subepithelial electron-dense deposits were found after three days and were still visible on day 14. Proteinuria starte d within the first 24 hours despite the absence of an immune response at this time and was still present on day 14. Similar results were obs erved in immune deficient athymic nude rats in the early phase. Perfus ion of heparin after NPtase inhibited the deposition of IgG and C3 and prevented proteinuria in naive but not in actively immunized rats. Th is result provides further evidence that specific antibodies to NPtase were not involved in the immune complex-like deposits seen in the ear ly phase. NPtase is a novel molecule, as it reveals both high affinity for the GEM and binding of circulating immunoglobulins, by a non-anti gen-antibody mechanism, to form IC-like deposits on the GEM. These dep osits are capable of activating the complement system, thus triggering a series of events leading to glomerulonephritis. These results delin eate an additional pathway for the pathogenesis of ICGN related to bac terial infection.