Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1984 Nov;74(5):1850–1859. doi: 10.1172/JCI111604

Electrical charge of the antigen determines intraarticular antigen handling and chronicity of arthritis in mice.

W B van den Berg, L B van de Putte, W A Zwarts, L A Joosten
PMCID: PMC425365  PMID: 6501574

Abstract

We studied the influence of antigenic charge on the handling of intraarticular antigen by the joint and on the ability of the antigen to induce chronic arthritis. Three different antigens were used: anionic native bovine serum albumin (BSA), and charge modified BSA made cationic (pI 8.5) either by methylation (mBSA), or amidation (aBSA). 125I-labeled antigen was injected into the knee joints of nonimmune mice and of mice immunized with antigen in Freund's complete adjuvant. Intraarticular antigen retention of the cationic antigens mBSA and aBSA was significantly increased compared with native BSA, both in immune and non-immune mice. In vitro studies indicated the electrostatic character of the binding of the cationic antigens to joint tissues and confirmed the large difference in antigen retention of the antigens found in vivo. A 100-fold amount of cationic antigen could be bound to non-cartilaginous collagenous tissue of the joint compared with antibody-mediated trapping of native BSA, and for hyaline articular cartilage, this difference was even greater. In immunized mice, chronic arthritis only developed after intraarticular injection of the cationic antigens. This phenomenon was apparently related to increased retention of mBSA and aBSA compared with BSA, since delayed hypersensitivity and humoral immunity were comparable for the three antigens used. Our data indicate that antigenic charge is an important determinant of antigen handling by the joint and, in addition, support the concept that the development of chronic arthritis depends on the amount of antigen retained in the joint.

Full text

PDF
1850

Images in this article

1853Image
on p.1853

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adler S. G., Wang H., Ward H. J., Cohen A. H., Border W. A. Electrical charge. Its role in the pathogenesis and prevention of experimental membranous nephropathy in the rabbit. J Clin Invest. 1983 Mar;71(3):487–499. doi: 10.1172/JCI110793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aston W. P., Ward T. L., Cooke T. D. The specific in vitro antibody-mediated retention of bovine serum albumin by porcine hyaline articular cartilage. Clin Exp Immunol. 1983 May;52(2):280–286. [PMC free article] [PubMed] [Google Scholar]
  3. Batsford S. R., Takamiya M., Vogt A. A model of in situ immune complex glomerulonephritis in the rat employing cationized ferritin. Clin Nephrol. 1980 Nov;14(5):211–216. [PubMed] [Google Scholar]
  4. Border W. A., Ward H. J., Kamil E. S., Cohen A. H. Induction of membranous nephropathy in rabbits by administration of an exogenous cationic antigen. J Clin Invest. 1982 Feb;69(2):451–461. doi: 10.1172/JCI110469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brackertz D., Mitchell G. F., Mackay I. R. Antigen-induced arthritis in mice. I. Induction of arthritis in various strains of mice. Arthritis Rheum. 1977 Apr;20(3):841–850. doi: 10.1002/art.1780200314. [DOI] [PubMed] [Google Scholar]
  6. Cooke T. D., Hurd E. R., Jasin H. E., Bienenstock J., Ziff M. Identification of immunoglobulins and complement in rheumatoid articular collagenous tissues. Arthritis Rheum. 1975 Nov-Dec;18(6):541–551. doi: 10.1002/art.1780180603. [DOI] [PubMed] [Google Scholar]
  7. Cooke T. D., Hurd E. R., Ziff M., Jasin H. E. The pathogenesis of chronic inflammation in experimental antigen-induced arthritis. II. Preferential localization of antigen-antibody complexes to collagenous tissues. J Exp Med. 1972 Feb 1;135(2):323–338. doi: 10.1084/jem.135.2.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Crowle A. J., Patrucco A. Preferential development by mice of delayed hypersensitivity to purified basic proteins. J Allergy. 1968 Sep;42(3):140–156. doi: 10.1016/0021-8707(68)90087-7. [DOI] [PubMed] [Google Scholar]
  9. Danon D., Goldstein L., Marikovsky Y., Skutelsky E. Use of cationized ferritin as a label of negative charges on cell surfaces. J Ultrastruct Res. 1972 Mar;38(5):500–510. doi: 10.1016/0022-5320(72)90087-1. [DOI] [PubMed] [Google Scholar]
  10. Faaber P., Capel P. J., Rijke G. P., Vierwinden G., van de Putte L. B., Koene R. A. Cross-reactivity of anti-DNA antibodies with proteoglycans. Clin Exp Immunol. 1984 Mar;55(3):502–508. [PMC free article] [PubMed] [Google Scholar]
  11. Gall E. P., Gall E. A. Histopathogenesis of bovine serum. Albumin-induced arthritis in the rabbit. J Rheumatol. 1980 Jan-Feb;7(1):13–23. [PubMed] [Google Scholar]
  12. Glynn L. E. The chronicity of inflammation and its significance in rheumatoid arthritis. Ann Rheum Dis. 1968 Mar;27(2):105–121. doi: 10.1136/ard.27.2.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  14. Hasselbacher P., Nacht J. L., Labosky D. A., Steinberg M. E. Antigen-induced arthritis: an immunohistologic study of articular tissue and synovial fluid using the horseradish peroxidase technique. J Rheumatol. 1980 Sep-Oct;7(5):596–608. [PubMed] [Google Scholar]
  15. Hollister J. R., Mannik M. Antigen retention in joint tissues in antigen-induced synovitis. Clin Exp Immunol. 1974 Apr;16(4):615–627. [PMC free article] [PubMed] [Google Scholar]
  16. Ishikawa H., Smiley J. D., Ziff M. Electron microscopic demonstration of immunoglobulin deposition in rheumatoid cartilage. Arthritis Rheum. 1975 Nov-Dec;18(6):563–576. doi: 10.1002/art.1780180606. [DOI] [PubMed] [Google Scholar]
  17. Jasin H. E. Mechanism of trapping of immune complexes in joint collagenous tissues. Clin Exp Immunol. 1975 Dec;22(3):473–485. [PMC free article] [PubMed] [Google Scholar]
  18. Katsura Y. Cell-mediated and humoral immune responses in mice. III. Dynamic balance between delayed-type hypersensitivity and antibody response. Immunology. 1977 Mar;32(3):227–235. [PMC free article] [PubMed] [Google Scholar]
  19. Katsura Y., Nakano K., Kabara Y., Uesaka I. Cell-mediated and humoral immune responses in mice. I. Necessary conditions for the detection of delayed-type hypersensitivity. Int Arch Allergy Appl Immunol. 1977;53(2):152–161. doi: 10.1159/000231746. [DOI] [PubMed] [Google Scholar]
  20. Kruijsen M. W., van den Berg W. B., van de Putte L. B., van den Broek W. J. Detection and quantification of experimental joint inflammation in mice by measurement of 99mTc-pertechnetate uptake. Agents Actions. 1981 Dec;11(6-7):640–642. doi: 10.1007/BF01978775. [DOI] [PubMed] [Google Scholar]
  21. Lens J. W., van den Berg W. B., van de Putte L. B. Flare-up of antigen-induced arthritis in mice after challenge with intravenous antigen: studies on the characteristics of and mechanisms involved in the reaction. Clin Exp Immunol. 1984 Feb;55(2):287–294. [PMC free article] [PubMed] [Google Scholar]
  22. Lens J. W., van den Berg W. B., van de Putte L. B. Quantitation of arthritis by 99mTc-uptake measurements in the mouse knee-joint: correlation with histological joint inflammation scores. Agents Actions. 1984 Jun;14(5-6):723–728. doi: 10.1007/BF01978915. [DOI] [PubMed] [Google Scholar]
  23. Malamud D., Drysdale J. W. Isoelectric points of proteins: a table. Anal Biochem. 1978 Jun 1;86(2):620–647. doi: 10.1016/0003-2697(78)90790-x. [DOI] [PubMed] [Google Scholar]
  24. Stanescu R., Leibovich S. J. The negative charge of articular cartilage surfaces. An electron microscopic study using cationized ferritin. J Bone Joint Surg Am. 1982 Mar;64(3):388–398. [PubMed] [Google Scholar]
  25. Teuscher C., Donaldson D. M. The deposition and formation of immune complexes in collagenous tissues. Clin Immunol Immunopathol. 1979 May;13(1):56–66. doi: 10.1016/0090-1229(79)90020-5. [DOI] [PubMed] [Google Scholar]
  26. Tew J. G., Mandel T. E., Rice P. L. Immune elimination and immune retention: the relationship between antigen retained in the foot and the elicitation of footpad swelling. Immunology. 1980 Jul;40(3):425–433. [PMC free article] [PubMed] [Google Scholar]
  27. Vogt A., Rohrbach R., Shimizu F., Takamiya H., Batsford S. Interaction of cationized antigen with rat glomerular basement membrane: in situ immune complex formation. Kidney Int. 1982 Jul;22(1):27–35. doi: 10.1038/ki.1982.128. [DOI] [PubMed] [Google Scholar]
  28. van Beusekom H. J., van de Putte L. B., van den Berg W. B., van den Broek W. J., Buijs W. C. Antigen handling in antigen-induced joint inflammation: kinetics of a second intra-articularly injected dose of antigen in an already established antigen-induced joint inflammation. Immunology. 1981 Sep;44(1):153–161. [PMC free article] [PubMed] [Google Scholar]
  29. van den Berg W. B., Lens J. W., van de Putte L. B., van Beusekom H. J. Antigen induced arthritis: antigen handling and chronicity of joint inflammation. Agents Actions Suppl. 1982;11:233–241. [PubMed] [Google Scholar]
  30. van den Berg W. B., van Beusekom H. J., van de Putte L. B., Zwarts W. A., van der Sluis M. Antigen handling in antigen-induced arthritis in mice: an autoradiographic and immunofluorescence study using whole joint sections. Am J Pathol. 1982 Jul;108(1):9–16. [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES