We have shown that synthetic polycations bind to glomerular polyanion and alter permeability to macromolecules and immune complexes. Studies are proposed to examine if platelet/neutrophil activation and the consequent glomerular binding of released cationic proteins cause altered glomerular permeability to immune complexes during the early pathogenesis of glomerulonephritis. The studies will utilize the following experimental models: In the first, inflammatory cells will be activated by intrarenal arterial infusions of synthetic platelet-activating factor (PAF) or antigen in sensitized "IgE rabbits" to cause release of endogenous PAF from basophils. The effects of ensuing cationic protein release will be tested by measuring glomerular permeability to macromolecules and pre-formed soluble immune complexes. In the second, BSA will be infused into the renal arteries in BSA immunized rabbits. The immune complexes formed in vivo will act as triggers for cell activation and cationic protein release. In the third, the biology of inflammatory cell activation, cationic protein binding and immune complex deposition in glomeruli will be studied in the rabbit model of acute serum sickness. Pharmacologic interventions will be employed to blunt inflammatory cell activation (by prostacyclin-theophylline, ticlopidine, or anti-platelet/antineutrophil sera) or neutralize cationic proteins (by heparins) and thus attempt to decrease immune complex deposition. The emphasis is on events which lead to immune complex deposition and not on the well-characterized mechanisms of subsequent glomerular inflammation and damage.