Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1984 Jul 1;160(1):125–137. doi: 10.1084/jem.160.1.125

Clearance of circulating IgA immune complexes is mediated by a specific receptor on Kupffer cells in mice

PMCID: PMC2187430  PMID: 6736868

Abstract

To characterize the physiology of circulating IgA immune complexes (IgA- IC), the dynamics of IgA-IC removal by the liver were examined. After intravenous injection, covalently cross-linked IgA antibodies to the dinitrophenyl determinant were rapidly removed from the circulation by the liver. Immunofluorescence microscopy and light and electron microscope autoradiography showed that the IgA-IC were associated with Kupffer cells. With increasing doses of injected IgA-IC the clearance velocity approached a maximum, thus prolonging the circulation of IgA- IC. All these observations indicated a receptor-mediated process. Saturating doses of various potential receptor-blocking agents, heat- aggregated mouse IgG, microaggregated human serum albumin, and purified dimeric IgA did not influence the clearance pattern and hepatic uptake of radiolabeled IgA-IC. Mouse livers were also perfused via the portal vein with 1 microgram of IgA-IC. In the presence or absence of serum proteins, 43% of the perfused IgA-IC were removed in a single passage. This liver uptake was not reduced with simultaneous perfusion of large doses of aggregated mouse IgG, aggregated human serum albumin, or purified free dimeric mouse IgA. In contrast, the liver uptake of radiolabeled IgA-IC was decreased by 88% with the addition of 1 mg unlabeled IgA-IC. These observations support the conclusion that removal of IgA-IC from circulation is mediated by a specific IgA receptor on Kupffer cells.

Full Text

The Full Text of this article is available as a PDF (1.4 MB).

Selected References

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

  1. Brown T. A., Russell M. W., Mestecky J. Hepatobiliary transport of IgA immune complexes: molecular and cellular aspects. J Immunol. 1982 May;128(5):2183–2186. [PubMed] [Google Scholar]
  2. Delacroix D. L., Elkom K. B., Geubel A. P., Hodgson H. F., Dive C., Vaerman J. P. Changes in size, subclass, and metabolic properties of serum immunoglobulin A in liver diseases and in other diseases with high serum immunoglobulin A. J Clin Invest. 1983 Feb;71(2):358–367. doi: 10.1172/JCI110777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Della Corte E., Parkhouse R. M. Biosynthesis of immunoglobulin A (IgA). Secretion and addition of carbohydrate to monomer and polymer forms of a mouse myeloma protein. Biochem J. 1973 Nov;136(3):589–596. doi: 10.1042/bj1360589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dickler H. B., Kunkel H. G. Interaction of aggregated -globulin with B lymphocytes. J Exp Med. 1972 Jul 1;136(1):191–196. doi: 10.1084/jem.136.1.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Finbloom D. S., Abeles D., Rifai A., Plotz P. H. The specificity of uptake of model immune complexes and other protein aggregates by the murine reticuloendothelial system. J Immunol. 1980 Sep;125(3):1060–1065. [PubMed] [Google Scholar]
  6. Finbloom D. S., Plotz P. H. Studies of reticuloendothelial function in the mouse with model immune complexes. I. Serum clearance and tissue uptake in normal C3H mice. J Immunol. 1979 Oct;123(4):1594–1599. [PubMed] [Google Scholar]
  7. HELMKAMP R. W., GOODLAND R. L., BALE W. F., SPAR I. L., MUTSCHLER L. E. High specific activity iodination of gamma-globulin with iodine-131 monochloride. Cancer Res. 1960 Nov;20:1495–1500. [PubMed] [Google Scholar]
  8. Haakenstad A. O., Mannik M. Saturation of the reticuloendothelial system with soluble immune complexes. J Immunol. 1974 May;112(5):1939–1948. [PubMed] [Google Scholar]
  9. Hopf U., Brandtzaeg P., Hütteroth T. H., Meyer zum Büschenfelde K. H. In vivo and in vitro binding of IgA to the plasma membrane of hepatocytes. Scand J Immunol. 1978;8(6):543–549. doi: 10.1111/j.1365-3083.1978.tb00554.x. [DOI] [PubMed] [Google Scholar]
  10. Isaacs K., Miller F., Lane B. Experimental model for IgA nephropathy. Clin Immunol Immunopathol. 1981 Sep;20(3):419–426. doi: 10.1016/0090-1229(81)90152-5. [DOI] [PubMed] [Google Scholar]
  11. Jimenez R. A., Mannik M. Evaluation of aggregated IgG in mice as an Fc receptor specific probe of the hepatic mononuclear phagocyte system. Clin Exp Immunol. 1982 Jul;49(1):200–208. [PMC free article] [PubMed] [Google Scholar]
  12. Magilavy D. B., Rifai A., Plotz P. H. An abnormality of immune complex kinetics in murine lupus. J Immunol. 1981 Feb;126(2):770–774. [PubMed] [Google Scholar]
  13. Nagura H., Smith P. D., Nakane P. K., Brown W. R. IGA in human bile and liver. J Immunol. 1981 Feb;126(2):587–595. [PubMed] [Google Scholar]
  14. Nishi T., Bhan A. K., Collins A. B., McCluskey R. T. Effect of circulating immune complexes on Fc and C3 receptors of Kupffer cells in vivo. Lab Invest. 1981 May;44(5):442–448. [PubMed] [Google Scholar]
  15. Orlans E., Peppard J., Fry J. F., Hinton R. H., Mullock B. M. Secretory component as the receptor for polymeric IgA on rat hepatocytes. J Exp Med. 1979 Dec 1;150(6):1577–1581. doi: 10.1084/jem.150.6.1577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Peppard J., Orlans E., Payne A. W., Andrew E. The elimination of circulating complexes containing polymeric IgA by excretion in the bile. Immunology. 1981 Jan;42(1):83–89. [PMC free article] [PubMed] [Google Scholar]
  17. Pfaffenbach G., Lamm M. E., Gigli I. Activation of the guinea pig alternative complement pathway by mouse IgA immune complexes. J Exp Med. 1982 Jan 1;155(1):231–247. doi: 10.1084/jem.155.1.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Plotz P. H., Kimberly R. P., Guyer R. L., Segal D. M. Stable model immune complexes produced by bivalent affinity labeling haptens: in-vivo survival. Mol Immunol. 1979 Sep;16(9):721–729. doi: 10.1016/0161-5890(79)90013-0. [DOI] [PubMed] [Google Scholar]
  19. Prieels J. P., Pizzo S. V., Glasgow L. R., Paulson J. C., Hill R. L. Hepatic receptor that specifically binds oligosaccharides containing fucosyl alpha1 leads to 3 N-acetylglucosamine linkages. Proc Natl Acad Sci U S A. 1978 May;75(5):2215–2219. doi: 10.1073/pnas.75.5.2215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rifai A., Mannik M. Clearance kinetics and fate of mouse IgA immune complexes prepared with monomeric or dimeric IgA. J Immunol. 1983 Apr;130(4):1826–1832. [PubMed] [Google Scholar]
  21. Rifai A., Small P. A., Jr, Teague P. O., Ayoub E. M. Experimental IgA nephropathy. J Exp Med. 1979 Nov 1;150(5):1161–1173. doi: 10.1084/jem.150.5.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Silverstein S. C., Steinman R. M., Cohn Z. A. Endocytosis. Annu Rev Biochem. 1977;46:669–722. doi: 10.1146/annurev.bi.46.070177.003321. [DOI] [PubMed] [Google Scholar]
  23. Socken D. J., Simms E. S., Nagy B. R., Fisher M. M., Underdown B. J. Secretory component-dependent hepatic transport of IgA antibody-antigen complexes. J Immunol. 1981 Jul;127(1):316–319. [PubMed] [Google Scholar]
  24. Stockert R. J., Kressner M. S., Collins J. C., Sternlieb I., Morell A. G. IgA interaction with the asialoglycoprotein receptor. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6229–6231. doi: 10.1073/pnas.79.20.6229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Unkeless J. C., Fleit H., Mellman I. S. Structural Aspects and Heterogeneity of Immunoglobulin Fc Receptors. Adv Immunol. 1981;31:247–270. doi: 10.1016/s0065-2776(08)60922-0. [DOI] [PubMed] [Google Scholar]
  26. Woodroffe A. J., Clarkson A. R., Seymour A. E., Lomax-Smith J. D. Mesangial IgA nephritis. Springer Semin Immunopathol. 1982;5(3):321–332. doi: 10.1007/BF01892091. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES