Abstract
In the present study the clearance kinetics and tissue distribution of human polyclonal heat-aggregated serum IgA (AIgA) of different sizes in rats was studied after intravenous administration of 125I-AIgA. The 125I-AIgA of different sizes disappeared from the circulation in a biphasic manner with an initial rapid half-life (T1/2) and a second slower T1/2. The first T1/2 was related to the size of the 125I-AIgA: high molecular weight (MW) 125I-AIgA was cleared much faster than 125I-AIgA with a low MW. Relatively more degradation products were observed in blood when high MW 125I-AIgA were injected as compared to low MW 125I-AIgA. The AIgA were mainly taken up by the liver. Eight minutes after injection of high MW 125I-AIgA, 90% of the injected dose was found in the liver, whereas less than 2% was detected in the spleen. Very little activity was detectable in other organs, such as lungs, heart and kidneys. In the present study 1-3% of the injected 125I-AIgA were found in the bile. Analysis of this material revealed that low MW 125I-AIgA were transported more efficiently to the bile than high MW 125I-AIgA. To obtain more insight into the receptors involved in the clearance of 125I-AIgA, rats were pretreated with ovalbumin or asialofetuin. The clearance of 125I-AIgA of different sizes was inhibited when rats were pretreated with asialofetuin. Pretreatment with ovalbumin had no effect on the clearance rates of 125I-AIgA. These results suggest a role for carbohydrate receptors, which recognize glycoprotein-containing galactose terminal residues on Kupffer cells, in the clearance of 125I-AIgA.
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- Ashwell G., Harford J. Carbohydrate-specific receptors of the liver. Annu Rev Biochem. 1982;51:531–554. doi: 10.1146/annurev.bi.51.070182.002531. [DOI] [PubMed] [Google Scholar]
- 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]
- Coppo R., Basolo B., Piccoli G., Mazzucco G., Bulzomì M. R., Roccatello D., De Marchi M., Carbonara A. O., Barbiano di Belgiojoso G. IgA1 and IgA2 immune complexes in primary IgA nephropathy and Henoch-Schönlein nephritis. Clin Exp Immunol. 1984 Sep;57(3):583–590. [PMC free article] [PubMed] [Google Scholar]
- Delacroix D. L., Denef A. M., Acosta G. A., Montgomery P. C., Vaerman J. P. Immunoglobulins in rabbit hepatic bile: selective secretion of IgA and IgM and active plasma-to-bile transfer of polymeric IgA. Scand J Immunol. 1982 Oct;16(4):343–350. doi: 10.1111/j.1365-3083.1982.tb00733.x. [DOI] [PubMed] [Google Scholar]
- Delacroix D. L., Hodgson H. J., McPherson A., Dive C., Vaerman J. P. Selective transport of polymeric immunoglobulin A in bile. Quantitative relationships of monomeric and polymeric immunoglobulin A, immunoglobulin M, and other proteins in serum, bile, and saliva. J Clin Invest. 1982 Aug;70(2):230–241. doi: 10.1172/JCI110610. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fanger M. W., Shen L., Pugh J., Bernier G. M. Subpopulations of human peripheral granulocyes and monocytes express receptors for IgA. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3640–3644. doi: 10.1073/pnas.77.6.3640. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fisher M. M., Nagy B., Bazin H., Underdown B. J. Biliary transport of IgA: role of secretory component. Proc Natl Acad Sci U S A. 1979 Apr;76(4):2008–2012. doi: 10.1073/pnas.76.4.2008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gorter A., Hiemstra P. S., Klar-Mohamad N., van Es L. A., Daha M. R. Binding, internalization and degradation of soluble aggregates of human secretory IgA by resident rat peritoneal macrophages. Immunology. 1988 Aug;64(4):703–708. [PMC free article] [PubMed] [Google Scholar]
- Hiemstra P. S., Biewenga J., Gorter A., Stuurman M. E., Faber A., van Es L. A., Daha M. R. Activation of complement by human serum IgA, secretory IgA and IgA1 fragments. Mol Immunol. 1988 Jun;25(6):527–533. doi: 10.1016/0161-5890(88)90074-0. [DOI] [PubMed] [Google Scholar]
- Hiemstra P. S., Gorter A., Stuurman M. E., Van Es L. A., Daha M. R. Activation of the alternative pathway of complement by human serum IgA. Eur J Immunol. 1987 Mar;17(3):321–326. doi: 10.1002/eji.1830170304. [DOI] [PubMed] [Google Scholar]
- 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]
- Hsu S. M., Hsu P. L. Demonstration of IgA and secretory component in human hepatocytes. Gut. 1980 Nov;21(11):985–989. doi: 10.1136/gut.21.11.985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jackson G. D., Lemaître-Coelho I., Vaerman J. P., Bazin H., Beckers A. Rapid disappearance from serum of intravenously injected rat myeloma IgA and its secretion into bile. Eur J Immunol. 1978 Feb;8(2):123–126. doi: 10.1002/eji.1830080210. [DOI] [PubMed] [Google Scholar]
- Jones A. L., Hradek G. T., Schmucker D. L. Intracellular processing of human vs. rat immunoglobulin A in the rat liver. Hepatology. 1985 Nov-Dec;5(6):1172–1178. doi: 10.1002/hep.1840050618. [DOI] [PubMed] [Google Scholar]
- Kauffmann R. H., Herrmann W. A., Meÿer C. J., Daha M. R., Van Es L. A. Circulating IgA-immune complexes in Henoch-Schönlein purpura. A longitudinal study of their relationship to disease activity and vascular deposition of IgA. Am J Med. 1980 Dec;69(6):859–866. doi: 10.1016/s0002-9343(80)80011-8. [DOI] [PubMed] [Google Scholar]
- Kijlstra A., Knutson D. W., Daha M. R., van Es L. A. Clearance and glomerular localization of preformed DNP anti-DNP immune complexes. Scand J Immunol. 1979;10(5):421–429. doi: 10.1111/j.1365-3083.1979.tb01371.x. [DOI] [PubMed] [Google Scholar]
- Kijlstra A., Knutson D. W., van der Lelij A., van Es L. A. Characteristics of soluble immune complexes prepared from oligovalent DNP conjugates and anti-DNP antibodies. J Immunol Methods. 1977;17(3-4):263–277. doi: 10.1016/0022-1759(77)90109-0. [DOI] [PubMed] [Google Scholar]
- Kolb H., Vogt D., Herbertz L., Corfield A., Schauer R., Schlepper-Schäfer J. The galactose-specific lectins on rat hepatocytes and Kupffer cells have identical binding characteristics. Hoppe Seylers Z Physiol Chem. 1980 Nov;361(11):1747–1750. [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lemaître-Coelho I., Altamirano G. A., Barranco-Acosta C., Meykens R., Vaerman J. P. In vivo experiments involving secretory component in the rat hepatic transfer of polymeric IgA from blood into bile. Immunology. 1981 Jun;43(2):261–270. [PMC free article] [PubMed] [Google Scholar]
- Lesavre P., Digeon M., Bach J. F. Analysis of circulating IgA and detection of immune complexes in primary IgA nephropathy. Clin Exp Immunol. 1982 Apr;48(1):61–69. [PMC free article] [PubMed] [Google Scholar]
- March S. C., Parikh I., Cuatrecasas P. A simplified method for cyanogen bromide activation of agarose for affinity chromatography. Anal Biochem. 1974 Jul;60(1):149–152. doi: 10.1016/0003-2697(74)90139-0. [DOI] [PubMed] [Google Scholar]
- Mestecky J., McGhee J. R. Immunoglobulin A (IgA): molecular and cellular interactions involved in IgA biosynthesis and immune response. Adv Immunol. 1987;40:153–245. doi: 10.1016/s0065-2776(08)60240-0. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Phillips J. O., Russell M. W., Brown T. A., Mestecky J. Selective hepatobiliary transport of human polymeric IgA in mice. Mol Immunol. 1984 Oct;21(10):907–914. doi: 10.1016/0161-5890(84)90147-0. [DOI] [PubMed] [Google Scholar]
- 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]
- Rifai A., Mannik M. Clearance of circulating IgA immune complexes is mediated by a specific receptor on Kupffer cells in mice. J Exp Med. 1984 Jul 1;160(1):125–137. doi: 10.1084/jem.160.1.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rits M., Cormont F., Bazin H., Meykens R., Vaerman J. P. Rat monoclonal antibodies. VI. Production of IgA secreting hybridomas with specificity for the 2,4-dinitrophenyl (DNP) hapten. J Immunol Methods. 1986 May 1;89(1):81–87. doi: 10.1016/0022-1759(86)90034-7. [DOI] [PubMed] [Google Scholar]
- Rits M., Kints J. P., Bazin H., Vaerman J. P. Rat C3 conversion by rat anti-2,4,dinitrophenyl (DNP) hapten IgA immune precipitates. Scand J Immunol. 1987 Apr;25(4):359–366. doi: 10.1111/j.1365-3083.1987.tb02201.x. [DOI] [PubMed] [Google Scholar]
- Sancho J., González E., Rivera F., Escanero J. F., Egido J. Hepatic and kidney uptake of soluble monomeric and polymeric IgA aggregates. Immunology. 1984 May;52(1):161–167. [PMC free article] [PubMed] [Google Scholar]
- Schiff J. M., Fisher M. M., Jones A. L., Underdown B. J. Human IgA as a heterovalent ligand: switching from the asialoglycoprotein receptor to secretory component during transport across the rat hepatocyte. J Cell Biol. 1986 Mar;102(3):920–931. doi: 10.1083/jcb.102.3.920. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Socken D. J., Jeejeebhoy K. N., Bazin H., Underdown B. J. Identification of secretory component as an IgA receptor on rat hepatocytes. J Exp Med. 1979 Dec 1;150(6):1538–1548. doi: 10.1084/jem.150.6.1538. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stahl P. D., Rodman J. S., Miller M. J., Schlesinger P. H. Evidence for receptor-mediated binding of glycoproteins, glycoconjugates, and lysosomal glycosidases by alveolar macrophages. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1399–1403. doi: 10.1073/pnas.75.3.1399. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Thornburg R. W., Day J. F., Baynes J. W., Thorpe S. R. Carbohydrate-mediated clearance of immune complexes from the circulation. A role for galactose residues in the hepatic uptake of IgG-antigen complexes. J Biol Chem. 1980 Jul 25;255(14):6820–6825. [PubMed] [Google Scholar]
- Tomana M., Kulhavy R., Mestecky J. Receptor-mediated binding and uptake of immunoglobulin A by human liver. Gastroenterology. 1988 Mar;94(3):762–770. doi: 10.1016/0016-5085(88)90252-1. [DOI] [PubMed] [Google Scholar]
- Underdown B. J., Schiff J. M. Immunoglobulin A: strategic defense initiative at the mucosal surface. Annu Rev Immunol. 1986;4:389–417. doi: 10.1146/annurev.iy.04.040186.002133. [DOI] [PubMed] [Google Scholar]
- Valentijn R. M., Kauffmann R. H., de la Rivière G. B., Daha M. R., Van ES L. A. Presence of circulating macromolecular IgA in patients with hematuria due to primary IgA nephropathy. Am J Med. 1983 Mar;74(3):375–381. doi: 10.1016/0002-9343(83)90954-3. [DOI] [PubMed] [Google Scholar]
- Vetvicka V., Fornůsek L., Kincade P. W., Kopecek J. Co-expression of different types of Fc receptors on murine peritoneal macrophages. Eur J Immunol. 1986 Aug;16(8):901–905. doi: 10.1002/eji.1830160805. [DOI] [PubMed] [Google Scholar]
