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The major Fc receptor in blood has a phosphatidylinositol anchor and is deficient in paroxysmal nocturnal haemoglobinuria

Abstract

Fc receptors on phagocytic cells in the blood mediate binding and clearance of immune complexes, phagocytosis of antibody-opsonized microorganisms, and potently trigger effector functions, including superoxide anion production and antibody-dependent cellular cytotoxicity. The Fc receptor type HI (FcγR III, CD 16), present in 135,000 sites per cell 1 on neutrophils and accounting for most of FcR in blood, unexpectedly has a phosphatidylinositol glycan (PIG) membrane anchor. Deficiency of FcγR III is observed in paroxysmal nocturnal haemoglobinuria (PNH), an acquired abnormality of haematopoietic cells2 affecting PIG tail biosynthesis or attachment3, and is prbably responsible for circulating immune complexes4 and susceptibility to bacterial infections associated with this disease5. Although a growing number of eukaryotic cell-surface proteins with PIG-tails are being described6,7, none has thus far been implicated in receptor-mediated endocytosis or in triggering of cell-mediated killing. Our findings on the FcγR III raise the question of how a PIG-tailed protein important in immune complex clearance in vivo8,9 and in antibody-dependent killing10 mediates ligand internalization and cytotoxicity. Together with our results, previous functional studies on FcγR III and FcγR II11,12 suggest that these two receptors may cooperate and that the type of membrane anchor is an important mechanism whereby the functional capacity of surface receptors can be regulated.

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References

  1. Fleit, H. B., Wright, S. D. & Unkeless, J. C. Proc. natn. Acad. Sci. U.S.A. 79, 3275–3279 (1982).

    Article  ADS  CAS  Google Scholar 

  2. Rosse, W. F. & Parker, C. J. Clin. Haemat. 14, 105–125 (1985).

    CAS  PubMed  Google Scholar 

  3. Low, M. G. Biochem. J. 244, 1–13 (1987).

    Article  CAS  Google Scholar 

  4. Villaescusa, R. Acta haemat. 68, 136–141 (1982).

    Article  CAS  Google Scholar 

  5. Crosby, W. H. Blood 8, 769–812 (1953).

    CAS  PubMed  Google Scholar 

  6. Low, M. G. & Saltiel, A. R. Science 239, 268–275 (1988).

    Article  ADS  CAS  Google Scholar 

  7. Ferguson, M. A. J. & Williams, A. F. A. Rev. Biochem. (in the press).

  8. Clarkson, S. B., Bussel, J. B., Kimberley, R. P., Valinsky, J. E., Nachman, R. L. & Unkeless, J. C. N. Engl. J. Med. 314, 123–129 (1986).

    Article  Google Scholar 

  9. Clarkson, S. B. et al. J. exp. Med. 164, 474–489 (1986).

    Article  CAS  Google Scholar 

  10. Perussia, B. et al. J. Immun. 130, 2142–2148 (1983).

    CAS  PubMed  Google Scholar 

  11. Shen, L., Gure, M. & Fanger, M. W. J. Immun. 139, 534–538 (1987).

    CAS  PubMed  Google Scholar 

  12. Graziano, R. F. & Fanger, M. W. J. Immun. 139, 3536–3541 (1987).

    CAS  PubMed  Google Scholar 

  13. Anderson, C. L. & Looney, R. J. Immun. Today 7, 264–266 (1986).

    Article  CAS  Google Scholar 

  14. Tetteroo, P. A. T., Van Der Schoot, C. E., Visser, F. J., Bos, M. J. E. & Von deme Borne, A. E. G. in Leucocyte typing III (eds McMichael, A. J. et al.) 702–706 (Oxford University Press, Oxford, 1987).

    Google Scholar 

  15. Nicholson-Weller, A., Spicer, D. B. & Austen, K. F. New Engl. J. Med. 312, 1091–1097 (1985).

    Article  CAS  Google Scholar 

  16. Kinoshita, T., Medof, M. E., Silber, R. & Nussenzweig, V. J. exp. Med. 162, 75–92 (1985).

    Article  CAS  Google Scholar 

  17. Stuart, S. G. et al. J. exp. Med. 166, 1668–1684 (1987).

    Article  CAS  Google Scholar 

  18. Werner, G. et al. in Leukocyte Typing II (eds Reinherz, E. L., Haynes, B. F., Nadler, L. M. & Bernstein, I. D.) 109–121 (Springer, New York, 1986).

    Book  Google Scholar 

  19. Khayat, D. et al. J. immunol. Meth. 100, 235–241 (1987).

    Article  CAS  Google Scholar 

  20. Reiser, H. et al. Cell 47, 365–370 (1986).

    Article  CAS  Google Scholar 

  21. Kroczek, R. A., Gunter, K. C., Seligman, B. & Shevach, E. M. J. Immun. 136, 4379–4384 (1986).

    CAS  Google Scholar 

  22. Looney, R. J. et al. J. exp. Med. 163, 826–836 (1986).

    Article  CAS  Google Scholar 

  23. Karas, S. P., Rosse, W. F. & Kurlander, R. J. Blood 60, 1277–1282 (1982).

    CAS  PubMed  Google Scholar 

  24. Vaughan, M., Taylor, M. & Mohankumar, T. J. Immun. 135, 4059–4065 (1985).

    Google Scholar 

  25. Williams, W. J., Beutler, E., Erselev, A. J. & Lichtman, M. N. Hematology (McGraw-Hill, New York, 1983).

    Google Scholar 

  26. Miller, L. J., Bainton, D. F., Borregaard, N. & Springer, T. A. J. clin. Invest. 80, 535–544 (1987).

    Article  CAS  Google Scholar 

  27. Anderson, C. L. et al. J. immun. 261, 12856–12864 (1986).

    CAS  Google Scholar 

  28. Fraker, P. J. & Speck, J. C. Biochem. biophys. Res. Commun. 80, 849–857 (1978).

    Article  CAS  Google Scholar 

  29. Laemmli, U. K. Nature 227, 680–685 (1970).

    Article  ADS  CAS  Google Scholar 

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Selvaraj, P., Rosse, W., Silber, R. et al. The major Fc receptor in blood has a phosphatidylinositol anchor and is deficient in paroxysmal nocturnal haemoglobinuria. Nature 333, 565–567 (1988). https://doi.org/10.1038/333565a0

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