Modified immunogold labelling applied to the study of protein droplets in glomerular disease

Abstract

Glomerular protein droplets have been observed in human glomerular epithelial cells, peripolar cells and mesangial cells, particularly in the preeclamptic lesion. Although morphologically similar, their functional role is uncertain. Whilst previous electron microscopic studies have shown these droplets to be generally uniform in electron density, our immunoelectron microscopy study of 10 biopsies, one showing lesions of preeclampsia, and the remaining 9 showing different forms of glomerular disease, generally displayed two distinct patterns of electron density and immunolabelling, when using a less severe fixation regime. An electron dense inner core was strongly positive to anti-fibrinogen, whilst a less dense peripheral zone was positive to anti-IgM. All other immunoglobulins, C3c, and albumin showed a less specific immunolabelling pattern. Protein droplets were also observed in proximal tubules in 7 out of 10 biopsies. In droplets found in most tubular cells immunolabelling was not partitioned, the most prominent findings being diffuse labelling for fibrinogen and albumin. In most instances where glomerular droplets were found adjacent to intraglomerular deposits, the marker identified within the deposit could also be seen in either the core area or the peripheral zone of the droplets. These findings raise the possibility that these droplets may be involved in protein adsorption from the deposits through a damaged glomerular basement membrane.