Experimental Glomerulonephritis

201

Sheep injected every 2 weeks with heterologous GBM and Freund's adjuvant by any one or combination of the following routes: intramuscular, subcutaneous, or intradermal, develop uniformly a fulminating, extracapillary glomerulonephritis, invariably fatal within 27 to 90 days after the first injection. The chief histologic feature is marked fibroepithelial proliferation of Bowman's capsule with crescent formation. The appearance of the lesions resembles the acute, subacute, and chronic stages of human glomerulonephritis, and depends on when the animal was sacrificed. Freund's adjuvant or heterologous GBM alone does not produce such a nephritis. The combination of placental tissue and Freund's adjuvant under the present experimental conditions was also unable to produce a nephritis. The clinical course, increase in nitrogen retention, evolution of renal lesions, and death, all describe a fulminating disease. The disease most characteristically resembles fatal, fulminating human subacute glomerulonephritis. The changes in serum proteins, decrease in serum albumin, and increase in serum globulin, occurred approximately the same in both the GBM-treated and the control adjuvant group. Similar changes have been reported from hyperimmunization alone, and so it is not clear how much these changes are due to immunization and how much is due to the nephritic process. The changes in serum cholesterol were not considered statistically significant. Circulating serum antibodies which localized (by fluorescent antibody technique in vitro) on basement membrane structures of the heterologous donor kidney antigen or which produced nephritis in the heterologous donor species (rat and dog) were found in serum of sheep sick or dying of nephritis. The passive transfer of nephritis by serum antibodies marks the first successful instance of transfer of nephritis by serum antibody to a heterologous species from an animal which had developed nephritis itself. The serum antibodies involved in the transfer of disease to the donor species appear to be unrelated to the mediators of nephritis in the sheep and may represent only the previously known heteronephrotoxic antibodies. By various biologic criteria the sheep nephritis presumably occurs by an autoimmune mechanism. However, it is not known whether the sheep nephritis is mediated by sensitized cells and/or antibodies. The latent period was estimated to end about 16 to 71 days after the first injection. Azotemia was estimated to begin about 17 to 78 days after the first injection. Proteinuria and azotemia began approximately 23 and 13 days before death. The rapid progression to a fatal termination defined the fulminating character of this disease.

Section: Glomierulonephritis Induced In Sheepmentioning

confidence: 93%

mentioning

confidence: 99%

Glomerulonephritis Induced in Sheep by Injections of Heterologous Glomerular Basement Membrane and Freund's Complete Adjuvant

Steblay

1962

201

“…In contrast, complex induced nephritis and nephrotoxic serum nephritis show preferential deposition of gamma globulin and complement in the capillary walls (17,30). AD also appears to differ from these other types of glomerular injury in that it features a marked proliferation of rnesangial ceils with only minor damage to the remainder of the capillary wall, while experimental complex-induced, nephrotoxic serum-induced, or naturally occurring human glomerulonephritis primarily affects the peripheral glomerular capillary wall with variable damage to the mesangial areas.…”

Section: Serum Proteinmentioning

confidence: 97%

“…In experimental animals it is known that amounts of antigen-antibody complexes too small to be detectable in the analytical ultracentrifuge are associated with the lesions of serum sickness and at least one type of experimental glomerulonephritis (28)(29)(30). In the AD-affected mink no direct evidence was found that the circulating protein-protein complexes were biologically harmful.…”

Section: Serum Proteinmentioning

confidence: 99%

Metabolism and Function of Gamma Globulin in Aleutian Disease of Mink

Porter

Dixon

Larsen

1965

Self Cite

Aleutian disease-affected mink, which are markedly hypergammaglobulinemic, show a decreased half-life of the serum gamma globulin indicating that the hyperglobulinemia is due to increased production. No evidence that the gamma globulin was antibody to the infectious agent, to autologous or isologous tissues, or to antigens the animal was responding to prior to development of the disease was obtained. The increased gamma globulin was found to be of the 6.4S variety, and gamma globulin containing protein-protein complexes of 9S to 17S and 22S to 25S classes were observed in serums of affected mink. The findings are most consistent with the Aleutian disease virus acting as a direct and somewhat selective stimulus to plasma cell proliferation. There is no evidence that the arterial and glomerular lesions of Aleutian disease have an immunologic pathogenesis. It seems possible that these vascular changes may be directly caused by the viral agent, or may be the result of the increased gamma globulin levels.

“…Abundant data derived from experimental models have shown that the presence of complexes in the circulation coincides temporally with the development of the lesions, e.g., acute glomerulonephritis and vasculitis (5,6) and chronic glomerulonephritis (7). In these studies the complexes were demonstrable in the lesions, and it was reasonably presumed that they reached their destination in the tissues after passage through the circulation.…”

Section: Platzs 21 and 22mentioning

confidence: 98%

Studies on Circulating Immune Complexes

Cochrane

Hawkins

1968

169

With the observations of immune complexes or antigens in the circulation of patients with rheumatoid arthritis (1, 2), systemic lupus erythematosus (3, 4), and other diseases, much attention has been drawn to their possible significance in the pathogenesis of the lesions in these disorders. Abundant data derived from experimental models have shown that the presence of complexes in the circulation coincides temporally with the development of the lesions, e.g., acute glomerulonephritis and vasculitis (5, 6) and chronic glomerulonephritis (7). In these studies the complexes were demonstrable in the lesions, and it was reasonably presumed that they reached their destination in the tissues after passage through the circulation.Previous studies in this series have analyzed the mechanisms by which circulating immune complexes are capable of localizing in vessel walls. It was found that complexes localized in blood vessd walls only during an increase in vascular permeability and that the complexes were trapped along the vascular basement membranes during the passage of plasma fluids through the permeable membrane (8). The increase of vascular permeability was brought about in particular by vasoactive amines and histamine that were released from their tissue reservoirs, the mast cells, by the action of the complexes themselves (9). The accompanying article presents data suggesting that this mechanism of localization is instrumental in serum sickness.The present paper deals with the physicochemical properties of complexes and with the concentration of complexes in the plasma required for detectable localization to occur. The validity of these findings is tested in experimental serum sickness of rabbits, a disease known to be caused by deposition of circulating immune complexes. A preliminary report has been presented (10).