The long term objective of the present proposal is to advance our understanding of the pathogenetic mechanisms involved in proteinuria of glomerular origin and immune-complex deposition/formation/precipitation. Emphasis will be laid on the molecular biology of various components of the glomerular capillary wall which apparently play a vital role in these mechanisms. The alterations in the capillary wall which occur during nephrotic or nephritic states will be determined. In vivo and in vitro interactions of exogenous and endogenous macromolecules with various components of the glomerular capillary wall will be investigated in order to delineate the mechanisms involved in the induction of proteinuria and immune complex deposition. A wide variety of techniques including electron microscopy, EM-autoradiography, freeze-fracture autoradiography, immunocytochemistry, chromatography, gel electrophoresis, sedimentation ultracentrifugal analysis and protein monolayer spreading rotary shadow techniques will be employed. It is anticipated that the execution of the experiments outlined in this investigation will provide certain answers to questions which are directly related to nephrotic and nephritic conditions in man.
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