マウス急性血清病腎炎における陽性滑荷電抗原の意義について―抗原の化学的修飾の役割―

小林 正貴; 小山 哲夫; 稲毛 博実; 成田 光陽; 東條 静夫

doi:10.14842/jpnjnephrol1959.27.1515

The effect of antigenic charge on the glomerular deposition of immune complexes in acute serum sickness nephritis in mice.

MASAKI KOEAYASHI, AKIO KOYAMA, HIROMI INAGE, MITSUHARU NARITA, SHIZUO TOJO

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Keywords: chemically modified cationic antigen, acute serum sickness nephritis, circulating immune complex deposition, in situ immune complex formation, subepithelial deposition

JOURNAL FREE ACCESS

1985 Volume 27 Issue 11 Pages 1515-1521

DOI https://doi.org/10.14842/jpnjnephrol1959.27.1515

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Published: 1985 Received: March 06, 1985 Available on J-STAGE: July 05, 2010 Accepted: - Advance online publication: - Revised: -
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Date of correction: July 05, 2010 Reason for correction: - Correction: DTRECEIVED Details: Right : 19850306

Date of correction: July 05, 2010 Reason for correction: - Correction: CITATION Details: Wrong : 1) Germuth, F. G.: A comparative histologic and immunologic study in rabbits of induced hypersensitvity of the serum sickness type. J. Exp. Med., 97: 257-293, 1953.
2) Dixon, F. J., Feldman, J. D. and Vazquez, J. J,: experimental glomerulonephritis. The pathogenesis of a laboratory model resembling the spectrum of human glomerulonephritis. J Exp. Med., 113: 899-921, 1961.
3) Vogt, A., Schmidt, U., Takamiya, H. and Ba-tsford, S. R.: In situ immune complex nephritis and basic proteins. Proc. Eur. Dial. Transplant Assoc., 17: 613-620, 1980.
4) Batsford, S. R., Takamiya, H. and Vogt, A.: A model of in situ immune complex glomerulone-phritis in the rat employing cationized ferritin Gun. Nephrol., 14: 211-216, 1980.
5) Couser, W. G. and Salant, D. J.: In situ immune complex formation and glomerular injury. Kidney Int., 17: 1-13, 1980.
6) Border, WA., Ward, H.J., Kamil, E.S. and Cohen, A. H.: Induction of membranous nephropathy in rabbits by administration of an exogenous cationic antigen. J. Clin. Invest., 69: 451-461, 1982.
9) Hoare, D. G. and Koshland, D. E.: A method for the quantitative modification and estimation of carboxylic acid groups in proteins. J Biol, Chem., 242: 2447-2453, 1967.
10) Minden, Po and Farr, R. S.: Ammonium sulphate method to measure antigen.binding capacity. In Handbook of Immunology. Blackwell Scientific Publications Oxford, England. 3rd edition. 1: 13.1-13.12, 1973.
11) Kuriyama, T.: Chronic glomerulonephritis induced by prolonged immunization in the rabbit. Lab. Invest., 28: 224-235, 1973.
13) Ram, J. S. and Maurer, P. H.: Modified Bovine Serum Albumin. VII. Studies on the role of free carboxyl groups of the protein in the interaction with its antibies. Arch. Biochem, Biophys., 83: 223-232, 1959.
14) Gallo, G. R., Caulin-Glaser, T.: and Lamm, M.E.: Charge of circulating immune complexes as a factor in glomerular basement membrane localization in mice. J. Gun. Invest., 61: 1305-1313, 1981.
16) Kanwar, Y. S. and Farquhar, M. G.: Anionic sites in the glomerular basement membrane. Inn vivo and in vitro localization to the laminae rara& by cationic probes. J Cell Biol., 81: 137-153, 1979.
17) Naruse, T., Kitamura, K., Miyakawa, Ym and. Sibata, S.: Deposition of renal tubular epitheliall antigen along the glomerular capillary walls of patients with membranous glomerulonephritis. J. Immunol., 110: 1163-1166, 1973.
18) Combes, B., Stastny, P., Shorey, J., Eigenbrodt, E. H., Barrera, A. and Hull, A. R.: Glomerulonephritis with deposition of Australia antigenantibody complexes in glomerular basement membrane. Lam ncet 2: 234-237, 1971.
19) Naruse, T.: Renal brush border antigen. Procm. 8th Int. Congr. Nephrol., 891-895, 1981.
20) Germuth, F, G., Rodriguez, E. R., Lorelle, C.A.,. Trump, E. I., Milano, L. L. and Wise, O.: Passive immune complex glomerulonephritis in mice: Models for various lesions found in human disease II. Low avidity complexes and diffuse prolif erative glomerulonephritis with subepithelial deposits.. Lab. Invest., 41: 366-371, 1979.
21) Iskandar, S. SS and Jennette, J. C.: Influence of antibody avidity on glomerular immune complex localization o Am. J Pathol., 112: 155-159, 1983.

Right : 1) Germuth, F. G.: A comparative histologic and immunologic study in rabbits of induced hypersensitvity of the serum sickness type. J. Exp. Med., 97: 257-293, 1953.
2) Dixon, F. J., Feldman, J. D. and Vazquez, J. J,: experimental glomerulonephritis. The pathogenesis of a laboratory model resembling the spectrum of human glomerulonephritis. J Exp. Med., 113: 899-921, 1961.
3) Vogt, A., Schmidt, U., Takamiya, H. and Ba-tsford, S. R.: In situ immune complex nephritis and basic proteins. Proc. Eur. Dial. Transplant Assoc., 17: 613-620, 1980.
4) Batsford, S. R., Takamiya, H. and Vogt, A.: A model of in situ immune complex glomerulone-phritis in the rat employing cationized ferritin Gun. Nephrol., 14: 211-216, 1980.
5) Couser, W. G. and Salant, D. J.: In situ immune complex formation and glomerular injury. Kidney Int., 17: 1-13, 1980.
6) Border, WA., Ward, H.J., Kamil, E.S. and Cohen, A. H.: Induction of membranous nephropathy in rabbits by administration of an exogenous cationic antigen. J. Clin. Invest., 69: 451-461, 1982.
9) Hoare, D. G. and Koshland, D. E.: A method for the quantitative modification and estimation of carboxylic acid groups in proteins. J Biol, Chem., 242: 2447-2453, 1967.
10) Minden, Po and Farr, R. S.: Ammonium sulphate method to measure antigen.binding capacity. In Handbook of Immunology. Blackwell Scientific Publications Oxford, England. 3rd edition. 1: 13.1-13.12, 1973.
11) Kuriyama, T.: Chronic glomerulonephritis induced by prolonged immunization in the rabbit. Lab. Invest., 28: 224-235, 1973.
13) Ram, J. S. and Maurer, P. H.: Modified Bovine Serum Albumin. VII. Studies on the role of free carboxyl groups of the protein in the interaction with its antibies. Arch. Biochem, Biophys., 83: 223-232, 1959.
14) Gallo, G. R., Caulin-Glaser, T.: and Lamm, M.E.: Charge of circulating immune complexes as a factor in glomerular basement membrane localization in mice. J. Gun. Invest., 61: 1305-1313, 1981.
16) Kanwar, Y. S. and Farquhar, M. G.: Anionic sites in the glomerular basement membrane. Inn vivo and in vitro localization to the laminae rara& by cationic probes. J Cell Biol., 81: 137-153, 1979.
17) Naruse, T., Kitamura, K., Miyakawa, Ym and. Sibata, S.: Deposition of renal tubular epitheliall antigen along the glomerular capillary walls of patients with membranous glomerulonephritis. J. Immunol., 110: 1163-1166, 1973.
18) Combes, B., Stastny, P., Shorey, J., Eigenbrodt, E. H., Barrera, A. and Hull, A. R.: Glomerulonephritis with deposition of Australia antigenantibody complexes in glomerular basement membrane. Lam ncet 2: 234-237, 1971.
19) Naruse, T.: Renal brush border antigen. Procm. 8th Int. Congr. Nephrol., 891-895, 1981.
20) Germuth, F, G., Rodriguez, E. R., Lorelle, C.A.,. Trump, E. I., Milano, L. L. and Wise, O.: Passive immune complex glomerulonephritis in mice: Models for various lesions found in human disease II. Low avidity complexes and diffuse prolif erative glomerulonephritis with subepithelial deposits.. Lab. Invest., 41: 366-371, 1979.
21) Iskandar, S. SS and Jennette, J. C.: Influence of antibody avidity on glomerular immune complex localization o Am. J Pathol., 112: 155-159, 1983.

Abstract

We examined the role of antigenic charge on the deposition of immune complexes (IC) in murine gloerulia Acute serum sickens nephritis was induced by injecting chemically modified cationic bovine serum albumin (cationic BSA). Controls were immunized with unmodified native BSA (native BSA), All mice were given a primary intraperitoneal immunization with 500 pg of the respective antigens plus Freund's complete adjuvant. After 14 days, we divided the mice into following three groups. The first group was bled and killed for the characterization of antisera and histologic studyo Second group was injected intravenously with 200 μg of ¹²⁵I-labeled each BSA and bled at 5 minutes for measuring the size of IC. Third group was killed at 15 minutes after the second injection for histologic study. In the former renal specimens, neither IC nor antigen was detected in all animals. After the challenge, mice immunized with cationic BSA showed capillary wall deposits of IgG, whereas those immunized with native BSA developed mesangial depositions of IgG. Antibody avidity values in cationic BSA group were significantly lower than those in native BSA group (P<0, 005). The sucrose density gradient ultracentrif ugation study showed that the size of IC in cationic BSA group was slightly larger than 7S. From the above results, we speculated that : 1) The IC depositions on the glomerular capillary walls result from circulating IC formation. 2) The IC composed of cationic BSA effectively binds to the polyanion layer of the glomerular basement membrane. 3) Chemically modified cationization alters the characteristics of BSA, thereby causing the formation of small sized IC.

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