The Production of Chronic Glomerulonephritis in Rats by the Injection of Rabbit Anti-Rat-Placenta Serum

Abstract

Recently interest in diseases which may result from specific antibodies acting in vivo has been intensified by the following observations: It has been demonstrated that injection of animals with antiserum prepared from homologous kidney results in progressive renal lesions (1-5). Glomerulonephritis in rats has resulted also from the action of autoantibodies following the injection of rat kidney mixed with killed streptococci (6). Furthermore, in man it has been established by the work on erythroblastosis foetalis (7) that specific cytotoxic antibodies may arise naturally and cause serious or fatal disease.The clinical picture of the toxemias of pregnancy has many points in common with acute glomerulonephritis; namely, the explosive development of albuminutia, cylindruria, olignria, and hypertension. There has long been speculation about the possible r61e of the placenta in the etiology of the toxemias. This organ, derived in part from the fertilized ovum, suggests an obvious source of antigen which might prove foreign to the mother and provoke the production of injurious antibodies. With the idea in mind to test the possible renal effect of such an antigen-antibody reaction, a series of experiments was undertaken in which rabbit anti-rat-placenta serum was injected into pregnant rats. Specific anti-placenta serum has been known to interrupt pregnancy in the guinea pig and rabbit since the observations of Dobrowolski in 1903 (8). Degeneration of the placentae and fetal death likewise were found to follow the injection of rabbit anti-rat-placenta serum in rats of the Long-Evans strain (9). However, no acute renal lesions were observed at autopsy in these animals which were sacrificed at term 9 days after the antiserum was given.Smadel and Swift (10) reported that rats of the Long-Evans strain injected with nephrotoxic serum, may require months to develop chronic glomerulonephritis. It therefore seemed of interest to allow animals injected with antiplacenta serum to remain under observation for a period of months in order to detect a possible eventual effect on the kidneys. The present paper reports these experiments controlled by studies on additional groups of rats which were injected with anti-rat-kidney serum, anti-rat-erythrocyte serum, antirat-serum serum, normal rabbit serum, or which were left untreated. A preliminary description of some of these results has already appeared (11,12). 211

Congenital Malformations Induced by Rabbit Antiserum against Rat Placental Glycoproteins Isolated by Concanavalin A Affinity Chromatography. Teratogenic Antibodies are Not Nephrotoxic

“…Later in a series of papers, dialyzed against distilled water and lyophilized. The washed plaSeegal and Loeb (13,14) and Loeb and Seegal (11) reported cental residue was extracted with 100 ml of 0.1 M Tris-HCl buffer resorption of rat fetuses and the development of nephritis in the pH 8.0 containing 1% sodium deoxycholate for 2 h with constant 973 Data obtained from this study suggest that different antibodies may be involved in nephrotoxic serum nephritis (Masugi nephritis) and experimental production of congenital malformations induced by heterologous antirat placenta antiserum. The teratogenic antibodies against the glycoprotein fraction obtained by concanavalin A affinity column were not nephrotoxic.…”

“…It is generally agreed that these antisera are abortifacient (5,8,14), nephrotoxic (II, 13,14) and teratogenic (4,12). Some experimental data attempting to clarify these biologic effects have been documented.…”

Isotopes in Immunology

“…It has been known for a long time that antisera could be obtained to a particular tissue, which would have a cytotoxic action on that tissue. Thus Smadel in 1936 (126) obtained rabbit antisera to rat kidney tissue which were nephro toxic when injected into rats, and other workers have since de monstrated the production of cytotoxic antisera to other organs, c. g. liver, lung and placenta (43,59,94,124). The demonstration that these cytotoxic antibodies actually localised in the tissue, how ever, had to await the use of 131I-labelled anti-rat-kidney antibodies by Pressman and Keighley in 1948 (111).…”

Observations on the Pregnant Rat Injected With Nephrotoxic Rabbit Anti-Rat Placenta Serum and Desoxycorticosterone Acetate

“…The remaining half of the animals in each group were observed over a 7 week period. The rabbit anti-rat placenta serum used was a pool made up of equal amounts of serum obtained from two rabbits immunized according to the method previously described (1). The serum, inactivated by heating to 56°C.…”