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FcαRI-positive liver Kupffer cells: Reappraisal of the function of immunoglobulin A in immunity

Nature Medicine volume 6, pages 680–685 (2000)Cite this article

Abstract

Despite the well-recognized involvement of immunoglobulin (Ig) A in mucosal immunity, the function of its receptor, FcαRI (CD89), is poorly understood. The ability of FcαRI to activate leukocytes seems to conflict with the proposed anti-inflammatory activity of secretory IgA. We show here that in a transgenic mouse model, inflammatory mediators induced expression of FcαRI on Kupffer cells, which enabled efficient phagocytosis in vivo of bacteria coated with serum IgA. Secretory IgA did not initiate phagocytosis. Therefore, interactions between serum IgA and FcαRI on Kupffer cells may provide a ‘second line of defense’ in mucosal immunity, by eliminating invasive bacteria entering through the portal circulation and thus preventing disease.

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Figure 1: Expression of FcαRI on Kupffer cells.
Figure 2: Kupffer cells expressing FcαRI mediate phagocytosis of bacteria coated with IgA.
Figure 3: Serum IgA mediates phagocytosis through FcαRI, in contrast to secretory IgA.
Figure 4: IgA in mucosal immunity.

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Acknowledgements

The authors thank T. Hesp for animal care, J. Duijs (Leiden University Medical Center) for technical assistance with high-performance liquid chromatography experiments, and M. Schipper (Department of Pathology, University Medical Center Utrecht) for advice on human liver biopsies. We thank L. Shen (Dartmouth Medical School, New Hampshire) and G. Vidarsson for reviewing the manuscript. TNF-α was a gift from W. Buurman (Maastricht University, The Netherlands). This work was supported by Netherlands Organization for Scientific Research grant 901-12-214.

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Authors and Affiliations

  1. Department of Immunology and Medarex Europe, University Medical Center Utrecht, Lundlaan 6, Utrecht, 3584 EA, The Netherlands

    Marjolein van Egmond, Annemiek B. van Spriel, Cora A. Damen & Jan G.J. van de Winkel

  2. Department of Pathology, Faculty of Veterinary Medicine, Yalelaan 1, Utrecht, 3508 TD, The Netherlands

    Evert van Garderen

  3. Division of Biopharmaceutics, LACDR, Sylvius Laboratories, Wassenaarseweg 72, Leiden, 2333 AL, The Netherlands

    Edwin S. van Amersfoort & Johan Kuiper

  4. Department of Nephrology, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands

    Ger van Zandbergen

  5. Department of Gastro-Enterology, University Medical Center Utrecht, Lundlaan 6, 3584 EA, Utrecht, The Netherlands

    Jan van Hattum

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Correspondence to Jan G.J. van de Winkel.

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van Egmond, M., van Garderen, E., van Spriel, A. et al. FcαRI-positive liver Kupffer cells: Reappraisal of the function of immunoglobulin A in immunity. Nat Med 6, 680–685 (2000). https://doi.org/10.1038/76261

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