ROLE OF POLYCATIONIC MEDIATORS IN GLOMERULONEPHRITIS

  • Barnes, Jeffrey L (PI)

Project: Research project

Project Details

Description

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.
StatusFinished
Effective start/end date1/1/8212/31/88

Funding

  • National Institutes of Health

ASJC

  • Medicine(all)

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