Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1997 Nov;110(2):226–232. doi: 10.1111/j.1365-2249.1997.tb08321.x

IgA nephropathy-specific expression of the IgA Fc receptors (CD89) on blood phagocytic cells

S TOYABE *,†, Y KUWANO *, K TAKEDA *, M UCHIYAMA †, T ABO *
PMCID: PMC2265504  PMID: 9367406

Abstract

We analysed the biochemical features of receptors for the Fc-region of IgA (FcαR, CD89) on blood monocytes and granulocytes of patients with IgA nephropathy (IgAN). FcαR on monocytes of IgAN were found to have a higher Mr (60-80kD) than those of control monocytes (50–75 kD) and granulocytes (55–75 kD) in both IgAN and controls as shown by immunoprecipitation analysis. Removal of N-linked carbohydrates from FcαR on monocytes of IgAN revealed a 32–36 kD protein core, the Mr of which was still higher than that of controls (28–32 kD). When FcaL transcripts were analysed by reverse-transcription-PCR, only one prominent band was visualized in PCR products from IgAN monocytes. Since the results thus far show that IgAN monocytes express FcαR protein and mRNA differently from granulocytes and control monocytes, PCR products were then cloned and sequenced. The predominant band in PCR products from IgAN monocytes was identical to that of the FcαR a.l transcript, and an additional 10 transcripts containing five novel transcripts were obtained from granulocytes and control monocytes. In three transcripts, we found an insertion sequence between the S2 and EC1 domains, suggesting the existence of a new exon. These results suggest a predominant usage of FcαR a.l among various transcripts of FcαR in IgAN monocytes.

Keywords: Fcα receptor, IgA receptor, IgA nephropathy

Full Text

The Full Text of this article is available as a PDF (839.5 KB).

References

  • 1.D'Amico G. The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med. 1987;64:709–27. [PubMed] [Google Scholar]
  • 2.Clarkson AR, Seymour AE, Thompson AJ, et al. IgA nephropathy: a syndrome of uniform morphology, diverse clinical features and uncertain prognosis. Clin Nephrol. 1977;8:459–71. [PubMed] [Google Scholar]
  • 3.Sinico RAA, Fornasieri N, Oreni S, et al. Polymeric IgA rheumatoid factor in idiopathic IgA mesangial nephropathy (Berger's disease) J Immunol. 1986;137:536–41. [PubMed] [Google Scholar]
  • 4.Czerkinsky C, Koopman WJ, Jackson S, et al. Circulating immune complexes and immunoglobulin A rheumatoid factor in patients with mesangial immunoglobulin A nephropathies. J Clin Invest. 1986;77:1931–8. doi: 10.1172/JCI112522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Roccatello D, Picciotto G, Coppo R, et al. The fate of aggregated immunoglobulin A injected in IgA nephropathy patients and healthy controls. Am J Kidney Dis. 1991;18:20–5. doi: 10.1016/s0272-6386(12)80285-x. [DOI] [PubMed] [Google Scholar]
  • 6.Roccatello D, Picciotto G, Ropolo R, et al. Kinetics and fate of IgA-IgG aggregates as a model of naturally occurring immune complexes in IgA nephropathy. Lab Invest. 1992;66:86–95. [PubMed] [Google Scholar]
  • 7.Roccatello D, Picciotto G, Torchio M, et al. Removal systems of immunoglobulin A and immunoglobulin A containing complexes in IgA nephropathy and cirrhosis patients. The role of asialoglycoprotein receptors. Lab Invest. 1993;69:714–23. [PubMed] [Google Scholar]
  • 8.Stockert RJ, Kressner MS, Collins JC, et al. IgA interaction with the asialoglycoprotein receptor. Proc Natl Acad Sci USA. 1982;79:6229–31. doi: 10.1073/pnas.79.20.6229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Monteiro RC, Kubagawa H, Cooper MD. Cellular distribution, regulation, and biochemical nature of an Fc alpha receptor in humans. J Exp Med. 1990;171:597–613. doi: 10.1084/jem.171.3.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Maliszewski CR, March CJ, Schoenborn MA, et al. Expression cloning of a human Fc receptor for IgA. J Exp Med. 1990;172:1665–72. doi: 10.1084/jem.172.6.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Allen AC, Harper SJ, Feehally J. Galactosylation of N- and O-linked carbohydrate moieties of IgAl and IgG in IgA nephropathy. Clin Exp Immunol. 1995;100:470–4. doi: 10.1111/j.1365-2249.1995.tb03724.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Kashem A, Endoh M, Nomoto Y, et al. Fc alpha R expression on polymorphonuclear leukocyte and superoxide generation in IgA nephropathy. Kidney Int. 1990;45:868–75. doi: 10.1038/ki.1994.114. [DOI] [PubMed] [Google Scholar]
  • 13.Kashem A, Endoh M, Nomoto Y, et al. Monocyte superoxide generation and its IgA-receptor in IgA nephropathy. Clin Nephrol. 1996;45:1–9. [PubMed] [Google Scholar]
  • 14.Monteiro RC, Grossetete B, Nguyen AT, et al. Dysfunctions of Fc alpha receptors by blood phagocytic cells in IgA nephropathy. Contrib Nephrol. 1995;111:116–22. [PubMed] [Google Scholar]
  • 15.Shen L. Receptors for IgA on phagocytic cells. Immunol Res. 1992;11:273–82. doi: 10.1007/BF02919133. [DOI] [PubMed] [Google Scholar]
  • 16.Monteiro RC, Hostoffer RW, Cooper MD, et al. Definition of immunoglobulin A receptors on eosinophils and their enhanced expression in allergic individuals. J Clin Invest. 1993;92:1681–5. doi: 10.1172/JCI116754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Monteiro RC, Cooper MD, Kubagawa H. Molecular heterogeneity of Fc alpha receptors detected by receptor-specific monoclonal antibodies. J Immunol. 1992;148:1764–70. [PubMed] [Google Scholar]
  • 18.Silvain C, Patry C, Launay P, et al. Altered expression of monocyte IgA Fc receptors is associated with defective endocytosis in patients with alcoholic cirrhosis. Potential role for IFN-gamma. J Immunol. 1995;155:1606–18. [PubMed] [Google Scholar]
  • 19.De Wit TP, Morton HC, Capel PJ, et al. Structure of the gene for the human myeloid IgA Fc receptor (CD89) J Immunol. 1995;155:1203–9. [PubMed] [Google Scholar]
  • 20.Patry C, Sibille Y, Lehuen A, et al. Identification of Fc alpha receptor (CD89) isoforms generated by alternative splicing that are differentially expressed between blood monocytes and alveolar macrophages. J Immunol. 1996;156:4442–8. [PubMed] [Google Scholar]
  • 21.Morton HC, Schiel AE, Janssen SW, et al. Alternatively spliced forms of the human myeloid Fc alpha receptor (CD89) in neutrophils. Immunogenetics. 1996;43:246–7. doi: 10.1007/BF00587311. [DOI] [PubMed] [Google Scholar]
  • 22.Pearson WR, Lipman DB. Improved tools for biological sequence comparison. Proc Natl Acad Sci USA. 1988;85:2444–8. doi: 10.1073/pnas.85.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Altschul SF, Gish W, Miller W, et al. Basic local alignment search tool. J Molec Biol. 1990;215:403–10. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  • 24.Senapathy P, Shapiro MB, Harris NL. Splice junctions, branch point sites, and exons: sequence statistics, identification, and applications to genome project. Meth Enzymol. 1990;183:252–78. doi: 10.1016/0076-6879(90)83018-5. [DOI] [PubMed] [Google Scholar]
  • 25.Davis W, Harrison PT, Hutchinson MJ, et al. Two distinct regions of FC gamma RI initiate separate signalling pathways involved in endocytosis and phagocytosis. EMBO Journal. 1990;14:432–41. doi: 10.1002/j.1460-2075.1995.tb07019.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Tepler I, Shimizu A, Leder P. The gene for the rat mast cell high affinity IgE receptor alpha chain. Structure and alternative mRNA splicing patterns. J Biol Chem. 1989;264:5912–5. [PubMed] [Google Scholar]
  • 27.Honjo T. Immunoglobulin genes. Ann Rev Immunol. 1983;1:499–528. doi: 10.1146/annurev.iy.01.040183.002435. [DOI] [PubMed] [Google Scholar]
  • 28.van de Winkel JG, Capel PJ. Human IgG Fc receptor heterogeneity: molecular aspects and clinical implications. Immunol Today. 1993;14:215–21. doi: 10.1016/0167-5699(93)90166-I. [DOI] [PubMed] [Google Scholar]
  • 29.von Heijne G. Patterns of amino acids near signal-sequence cleavage sites. Eur J Biochem. 1983;133:17–21. doi: 10.1111/j.1432-1033.1983.tb07424.x. [DOI] [PubMed] [Google Scholar]
  • 30.von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1983;14:4683–90. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Pang J, Taylor GR, Munroe DG, et al. Characterization of the gene for the human high affinity IgE receptor (Fc epsilon RI) alpha-chain. J Immunol. 1993;151:6166–74. [PubMed] [Google Scholar]
  • 32.Kulczycki A, Webber J, Soares HA, et al. Genomic organization of mouse Fc gamma receptor genes. Proc Natl Acad Sci USA. 1990;87:2856–60. doi: 10.1073/pnas.87.7.2856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.van de Winkel JG, Ernst LK, Anderson CJ, et al. Gene organization of the human high affinity receptor for IgG, Fc gamma RI (CD64). Characterization and evidence for a second gene. J Biol Chem. 1991;266:13449–55. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES