Staphylococcal neutral phosphatase (
NPtase) is a highly cationic bacterial surface bound
protein. It has significant affinity for human and rat
immunoglobulins in vitro and an electrostatic interaction may be involved. Radioisotopic studies showed that
NPtase had a high affinity for the polyanionic structures of the rat renal glomerulus. When the left kidneys of germ-free or naive (non-immune) Wistar rats were perfused with 80 micrograms of I125
NPtase, 21 micrograms of
NPtase were found in the left kidneys and 11 micrograms in the isolated glomeruli 15 minutes after perfusion. Deposits of autologous
immunoglobulin and C3 were seen in the glomeruli of rats immediately after perfusion with
NPtase (15 min) and persisted throughout the 14-day observation period. Histologically, neutrophil influx into the glomerulus was seen at 15 minutes and increased until three hours; subepithelial electron-dense deposits were found after three days and were still visible on day 14.
Proteinuria started 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 observed in immune deficient athymic nude rats in the early phase. Perfusion of
heparin after
NPtase inhibited the deposition of
IgG and C3 and prevented
proteinuria in naive but not in actively immunized rats. This result provides further evidence that specific
antibodies to
NPtase were not involved in the
immune complex-like deposits seen in the early phase.
NPtase is a novel molecule, as it reveals both high affinity for the GBM and binding of circulating
immunoglobulins, by a non-
antigen-antibody mechanism, to form IC-like deposits on the GBM. These deposits are capable of activating the
complement system, thus triggering a series of events leading to
glomerulonephritis. These results delineate an additional pathway for the pathogenesis of ICGN related to
bacterial infection.