Abstract
The principal objective of this investigation was to define the roles of injected and autogenous, kidney-localizing antibodies in the pathogenesis of rat nephrotoxic nephritis by relating data obtained with fluorescent antibody techniques to clinical and histologic observations. Such an analysis of the nephritis that developed in 28 rats after injection with the crude γ-globulin fraction of nephrotoxic serum has led us to the following conclusions:— The renal localization of nephrotoxic antibodies is primarily and, perhaps, exclusively in the membranes of the glomerular tufts. These antibodies are demonstrable, as antigens, in the glomeruli for up to 3 months after injection. In the acute stage of the nephritis, non-antibody, autogenous globulins are present in the glomerular tufts, probably as components of edema fluid. From 6 and 9 days to 3 months after injection, autogenous antibodies are localized in the glomerular tufts in a pattern that corresponds closely to that of the nephrotoxins. The essential requirements for the operation of the mechanism postulated by Kay are fulfilled in rat nephrotoxic nephritis.
Full Text
The Full Text of this article is available as a PDF (2.0 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BRAGDON J. H. Colorimetric determination of blood lipides. J Biol Chem. 1951 Jun;190(2):513–517. [PubMed] [Google Scholar]
- BUSH V., HEWITT R. E. Frozen sectioning; a new and rapid method. Am J Pathol. 1952 Sep-Oct;28(5):863–873. [PMC free article] [PubMed] [Google Scholar]
- COONS A. H., LEDUC E. H., CONNOLLY J. M. Studies on antibody production. I. A method for the histochemical demonstration of specific antibody and its application to a study of the hyperimmune rabbit. J Exp Med. 1955 Jul 1;102(1):49–60. doi: 10.1084/jem.102.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DEUTSCH H. F. II. Separation of antibody-active proteins from various animal sera by ethanol fractionation techniques. Methods Med Res. 1952;5:284–300. [PubMed] [Google Scholar]
- EHRICH W. E., FORMAN C. W., SEIFER J. Diffuse glomerular nephritis and lipid nephrosis; correlation of clinical, morphological, and experimental observations. AMA Arch Pathol. 1952 Nov;54(5):463–503. [PubMed] [Google Scholar]
- HEYMANN W., LUND H. Z. Nephrotic syndrome in rats. Pediatrics. 1951 May;7(5):691–706. [PubMed] [Google Scholar]
- HILL A. G. S., CRUICKSHANK B., CROSSLAND A. A study of antigenic components of kidney tissue. Br J Exp Pathol. 1953 Feb;34(1):27–34. [PMC free article] [PubMed] [Google Scholar]
- KORNGOLD L., LIPARI R. Tissue antigens of human tumors grown in rats, hamsters, and eggs. Cancer Res. 1955 Mar;15(3):159–161. [PubMed] [Google Scholar]
- KRAKOWER C. A., GREENSPON S. A. Localization of the nephrotoxic antigen within the isolated renal glomerulus. AMA Arch Pathol. 1951 Jun;51(6):629–639. [PubMed] [Google Scholar]
- Kay C. F. THE MECHANISM BY WHICH EXPERIMENTAL NEPHRITIS IS PRODUCED IN RABBITS INJECTED WITH NEPHROTOXIC DUCK SERUM. J Exp Med. 1940 Oct 31;72(5):559–572. doi: 10.1084/jem.72.5.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LIPPMAN R. W., MARTI H. U., CAMPBELL D. H. Nephrotoxic globulin nephritis. I. Course after a single intravenous injection. AMA Arch Pathol. 1952 Jan;53(1):1–14. [PubMed] [Google Scholar]
- MELLORS R. C., ARIAS-STELLA J., SIEGEL M., PRESSMAN D. Analytical pathology. II. Histopathologic demonstration of glomerular-localizing antibodies in experimental glomerulonephritis. Am J Pathol. 1955 Jul-Aug;31(4):687–715. [PMC free article] [PubMed] [Google Scholar]
- MELLORS R. C., SIEGEL M., PRESSMAN D. Analytic pathology: histochemical demonstration of antibody localization in tissues, with special reference to the antigenic components of kidney and lung. Lab Invest. 1955 Mar-Apr;4(2):69–89. [PubMed] [Google Scholar]
- PRESSMAN D., EISEN H. N., FITZGERALD P. J. The zone of localization of antibodies. VI. The rate of localization of anti-mouse-kidney serum. J Immunol. 1950 Apr;64(4):281–287. [PubMed] [Google Scholar]
- PRESSMAN D. The zone of localization of antibodies; the specific localization of antibodies to rat kidney. Cancer. 1949 Jul;2(4):697–700. doi: 10.1002/1097-0142(194907)2:4<697::aid-cncr2820020416>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
- Pressman D., Hill R. F., Foote F. W. The Zone of Localization of Anti-Mouse-Kidney Serum as Determined by Radioautographs. Science. 1949 Jan 21;109(2821):65–66. doi: 10.1126/science.109.2821.65. [DOI] [PubMed] [Google Scholar]
- SOLOMON D. H., GARDELLA J. W. Nephrotoxic nephritis in rats; evidence for the glomerular origin of the kidney antigen. J Exp Med. 1949 Sep;90(3):267–272. doi: 10.1084/jem.90.3.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smadel J. E. EXPERIMENTAL NEPHRITIS IN RATS INDUCED BY INJECTION OF ANTI-KIDNEY SERUM : I. PREPARATION AND IMMUNOLOGICAL STUDIES OF NEPHROTOXIN. J Exp Med. 1936 Nov 30;64(6):921–942. doi: 10.1084/jem.64.6.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smadel J. E. EXPERIMENTAL NEPHRITIS IN RATS INDUCED BY INJECTION OF ANTI-KIDNEY SERUM : III. PATHOLOGICAL STUDIES OF THE ACUTE AND CHRONIC DISEASE. J Exp Med. 1937 Mar 31;65(4):541–555. doi: 10.1084/jem.65.4.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smadel J. E., Farr L. E. EXPERIMENTAL NEPHRITIS IN RATS INDUCED BY INJECTION OF ANTI-KIDNEY SERUM : II. CLINICAL AND FUNCTIONAL STUDIES. J Exp Med. 1937 Mar 31;65(4):527–540. doi: 10.1084/jem.65.4.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smadel J. E., Farr L. E. The effect of diet on the pathological changes in rats with nephrotoxic nephritis. Am J Pathol. 1939 Mar;15(2):199–216.5. doi: 10.1111/j.1753-4887.1988.tb05436.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smadel J. E., Swift H. F. EXPERIMENTAL NEPHRITIS IN RATS INDUCED BY INJECTION OF ANTIKIDNEY SERUM : V. CHRONIC NEPHRITIS OF INSIDIOUS DEVELOPMENT FOLLOWING APPARENT RECOVERY FROM ACUTE NEPHROTOXIC NEPHRITIS. J Exp Med. 1941 Sep 30;74(4):345–358. doi: 10.1084/jem.74.4.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
- WEINREB M. S., SOULES K. H., WISSLER R. W. Quantitative studies of acute nephrotoxic nephritis in rats. Am J Pathol. 1954 Mar-Apr;30(2):311–335. [PMC free article] [PubMed] [Google Scholar]