ROLE OF POLYCATIONIC MEDIATORS GLOMERULOJNEPHRITIS

  • Barnes, Jeffrey L (PI)

Project: Research project

Project Details

Description

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) 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/anti-neutrophil sera or neutralize cationic
preoteins (by heparins) and thus attempt to decrease immune
complex deposition. In addition, a common feature of
glomerulonephritis is the development of hypercellularity as
the result of infiltration of blood-borne inflammatory cells
and/or the proliferation of resident glomerular cells. Studies
are proposed to examine the potential roles of biologically
active platelet cationic proteins in the recruitment of
inflammatory cells to glomerular structures and/or the
proliferation of resident glomerular cells in immune and
non-immune models of progressive glomerular disease.
Glomerular hypercellularity will be induced by: (1) Formation
of large intraglomerular immune complexes and by infusion of
BSA in preimmunized rabbit as outlined above; (2) Surgical
ablation of 1 and 5/6 of the total renal mass leading to
hyperfiltration of the remnant kidney; (3)
Desoxycorticosterose-salt induced hypertension; and (4)
Intravenous administration of Habu snake venom. Therapeutic
interventions with the anti-platelet drug ticlopidine,
anti-platelet serum and heparin will be employed to blunt
platelet activation and attempt to ameliorate glomerular
hypercellularity.
StatusFinished
Effective start/end date9/1/8611/30/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $118,076.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $127,712.00

ASJC

  • Medicine(all)

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