Factors influencing the removal of immune complex deposits from the renal glomerulus
This thesis describes a study of the mechanisms involved in the elimination of established, morphologically identifiable electron dense deposits from the glomeruli of rats with chronic serum sickness. The initial experiments established the experimental model and evaluated the effects of variations in the method of administration, the antigen dose and charge, and the route of administration. The model was further characterized in terms of the progression of the morphological, functional and biochemical abnormalities induced. Methods were developed to measure the amount of radio-labeled antigen in isolated glomeruli, and to measure the volume fraction of the electron dense deposits in glomeruli. Study was then limited to the first two weeks of recovery from chronic serum sickness, after injections of antigen have ceased, to ascertain the rates at which the antigen and deposits were removed. The influence of a variety of forms of intervention during this recovery period was then assessed. Manoeuvres which increased the level of circulating anti-BSA antibody were found to inhibit the removal of antigen and deposits from glomeruli. This effect was confirmed by passive immunization with immune rat serum. Manoeuvres which increased the number or activity of glomerular macrophages had no detectable effect on the removal of antigen or deposits. In the absence of plasma complement, the removal of antigen virtually ceased after four days. Cobra venom factor treated rats had lower proteinuria than controls, despite having a heavier antigen load. Manoeuvres which altered the, glomerular filtration rate and renal haemodynamics did not alter the rate of removal of antigen or deposits; nor did the administration of highly cationic molecules. The administration of large doses of heparin enhanced the rate of removal of antigen from the glomerulus, though an effect on deposit volume was not detected.