The morphologic basis of proteinuria in experimental chronic serum sickness glomerulonephritis in rabbits was studied by light and electron microscopy using horseradish peroxidase (effective radius 30 A; mol. wt. 40,000) and ferritin (effective radius 60 A; mol. wt. 480,000) as protein tracers. It was found that more ferritin, but paradoxically, less horseradish peroxidase gained access to the urinary space. Observations made by electron microscopy appeared to indicate a decreased permeability of most part of the damaged glomerular capillary wall to both tracers. These results favor the interpretation that proteinuria in chronic serum sickness glomerulonephritis is the result of focal rather than diffuse increase in permeability of the glomerular capillary wall. Lesions of segments of the nephron other than the glomerular capillary wall, may contribute to the leakage of proteins to the urinary space.

Annals of the New York Academy of SciencesVolume 254, Issue 1 p. 603-613 EXPERIMENTAL CHRONIC SERUM SICKNESS IN RABBITS THAT RECEIVED DAILY MULTIPLE AND HIGH DOSES OF ANTIGEN: A SYSTEMIC DISEASE* Jan R. Brentjens, Corresponding Author Jan R. Brentjens Departments of Microbiology and Pathology School of Medicine State University of New York Buffalo, New York 14214 †Recipient of a Fellowship of the American Society for Kidney Diseases. ‡Recipient of a Fellowship of the Max Kade Foundation.Search for more papers by this authorDave W. O'Connell, Dave W. O'Connell Departments of Microbiology and Pathology School of Medicine State University of New York Buffalo, New York 14214Search for more papers by this authorBoris Albini, Corresponding Author Boris Albini Departments of Microbiology and Pathology School of Medicine State University of New York Buffalo, New York 14214 †Recipient of a Fellowship of the American Society for Kidney Diseases. ‡Recipient of a Fellowship of the Max Kade Foundation.Search for more papers by this authorGiuseppe A. Andres, Giuseppe A. Andres Departments of Microbiology and Pathology School of Medicine State University of New York Buffalo, New York 14214Search for more papers by this author Jan R. Brentjens, Corresponding Author Jan R. Brentjens Departments of Microbiology and Pathology School of Medicine State University of New York Buffalo, New York 14214 †Recipient of a Fellowship of the American Society for Kidney Diseases. ‡Recipient of a Fellowship of the Max Kade Foundation.Search for more papers by this authorDave W. O'Connell, Dave W. O'Connell Departments of Microbiology and Pathology School of Medicine State University of New York Buffalo, New York 14214Search for more papers by this authorBoris Albini, Corresponding Author Boris Albini Departments of Microbiology and Pathology School of Medicine State University of New York Buffalo, New York 14214 †Recipient of a Fellowship of the American Society for Kidney Diseases. ‡Recipient of a Fellowship of the Max Kade Foundation.Search for more papers by this authorGiuseppe A. Andres, Giuseppe A. Andres Departments of Microbiology and Pathology School of Medicine State University of New York Buffalo, New York 14214Search for more papers by this author First published: June 1975 https://doi.org/10.1111/j.1749-6632.1975.tb29207.xCitations: 31 * Supported by United States Public Health Service Grant A1–10334. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 GERMUTH, F. G. & E. RODRIGUEZ. 1973. Immunopathology of the Renal Glomeiulus. Little, Brown and Company. Boston , Mass . 2 DIXON, F. J., J. D. FELDMAN & J. J. VAZQUEZ. 1961. J. Exp. Med. 113: 899. 3 FISH, A. J., A. F. MICHAEL & R. A. GOOD. 1971. In Diseases of the Kidney. M. B. Strauss & L. G. Welt, Eds.: 373. Little, Brown and Company. Boston , Mass . 4 ANDRES, G. A., B. C. SEEGAL, K. C. HSU, M. D. ROTHENBERG & M. L. CHAPEAU. 1963. J. Exp. Med. 117: 691. 5 WILSON, C. B. & F. J. DIXON. 1974. Annu. Rev. Med. 24: 83. 6 LONGCOPE, W. T. 1913. J. Exp. Med. 18: 678. 7 CLARK, E. & B. I. KAPLAN. 1937. Arch. Pathol. 24: 458. 8 DIXON, F. J. 1963. Harvey Lect. 58: 21. 9 BRENTJENS, J. R., D. W. O'CONNELL, I. B. PAWLOWSKI & G. A. ANDRES. 1974. Clin. Immunol. Immunopathol. 3: 112. 10 BRENTJENS, J. R., D. W. O'CONNELL, I. B. PAWLOWSKI, K. C. HSU & G. A. ANDRES. 1974. J. Exp. Med. 140: 105. 11 KOFFLER, D., P. H. SCHUR & H. G. KUNKEL. 1967. J. Exp. Med. 126: 607. 12 GAMBLE, C. N. 1974. Fed. Proc. 33: 3098. Citing Literature Volume254, Issue1Fifth International Conference on Immunofluorescence and Related Staining TechniquesJune 1975Pages 603-613 ReferencesRelatedInformation

Membranous and/or proliferative pneumonitis, similar in certain features to human interstitial pneumonitis, developed in rabbits making hyperactive antibody response to daily injections of bovine serum albumin (BSA) administered in multiple large doses sufficient to maintain the state of relative antigen-antibody equivalence. The pulmonary lesions were associated with deposition in alveolar capillary walls and interstitium of antigen, host globulin and complement, presumably in immune complexes. In some rabbits chronic interstitial pneumonitis, characterized by thickening of alveolar capillary walls, interstitial fibrosis and deposition of fibrinogen, was observed. The production of immune complex pneumonitis seems to depend on the degree of the antibody response because rabbits developing chronic serum sickness with low doses of BSA, rabbits with acute serum sickness as well as nonresponders showed no pulmonary alterations. This observation is comparable to that described by Dixon in his studies on experimental immune complex glomerulonephritis. It is conceivable that the pulmonary pathology shown here is produced by formation of larger amounts of complexes which may persist longer at critical levels in the circulation than in rabbits immunized with a single daily injection of BSA. In conclusion this study suggests: first, that experimental chronic serum sickness can be used as a model, not only for glomerulonephritis, but also for experimental systemic disease, comparable to human systemic diseases produced by circulating antigen-antibody complexes; and second, that the pathogenesis proposed here offers an alternative to using antilung basement membrane pneumonitis for the experimental approach to the study of human lung immunopathology.