Thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence

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Abstract

Plasmodium falciparum infected erythrocytes containing mature trophozoites and schizonts sequester along venular endothelium1 and are not in the peripheral circulation of patients with malaria. Knobs appear on infected erythrocytes and are the points of attachment to endothelium2. Sequestration may protect the parasite from splenic destruction3 and may play a role in the pathogenesis of cerebral malaria4. Correlates of sequestration have been developed in vitro using cultured human endothelium5 and an amelanotic melanoma cell line6. Knobless strains (K−) of P. falciparum fail to sequester in vivo and to bind to cells in vitro. We now present evidence that the receptor for cytoadherence is the glycoprotein, thrombospondin. Aotus monkey or human erythrocytes containing knobby (K+) but not Aotus erythrocytes containing knobless strains of P. falciparum bind to immobilized thrombospondin. Neither binds to the adhesive proteins laminin, fibronectin, factor VIII/von Wi lie brand factor or vitronectin. Both soluble thrombospondin and anti-thrombospondin antibodies inhibit binding of parasitized Aotus erythrocytes to immobilize thrombospondin and to melanoma cells which secrete thrombospondin.

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References

  1. 1

    Miller, L. H. Am. J. trop. Med. Hyg. 18, 860–865 (1969).

  2. 2

    Luse, S. A. & Miller, L. H. Am. J. trop. Med. Hyg. 20, 655–660 (1971).

  3. 3

    Barnwell, J. W., Howard, R. J. & Miller, L. H. Ciba Fdn Symp. 94, 117–136 (1983).

  4. 4

    Edington, G. M. Ann. trop. Med. Parasit. 48, 300–306 (1954).

  5. 5

    Udeinya, I. J., Schmidt, J. A., Aikawa, M., Miller, L. H. & Green, I. Science 213, 555–557 (1981).

  6. 6

    Schmidt, J. A. et al. J. clin. Invest. 70, 379–396 (1982).

  7. 7

    Baenziger, N. L., Brodie, G. N. & Majerus, P. W. Proc. natn. Acad. Sci. U.S.A. 68, 240–243 (1971).

  8. 8

    Phillips, D. R., Jennings, L. K. & Prasanna, H. R. J. biol. Chem. 255, 11629–11632 (1980).

  9. 9

    Yamada, K. M. A. Rev. Biochem. 52, 761–799 (1983).

  10. 10

    Timpl, R. et al. J. biol Chem. 254, 9933–9937 (1979).

  11. 11

    Hayman, E. G., Pierschbacher, M. D., Ohgren, Y. & Ruoslahti, E. Proc. natn. Acad. Sci. U.S.A. 80, 4003–4007 (1983).

  12. 12

    Hoyer, L. W., de los Santos, R. & Hoyer, J. R. J. clin. Invest. 52, 2737–2744 (1973).

  13. 13

    Udeinya, I. J., Graves, P. M., Carter, R., Aikawa, M. & Miller, L. H. Expl Parasit. 56, 207–214 (1983).

  14. 14

    Dixit, V. M. et al. Proc. natn. Acad. Sci. U.S.A. 82, 3472–3476 (1985).

  15. 15

    Roberts, D. D. et al. J. biol. Chem. 260, 9405–9411 (1985).

  16. 16

    Mosher, D. F., Doyle, M. J. & Jaffe, E. A. J. Cell Biol. 93, 343–348 (1982).

  17. 17

    Raugi, G. J., Mumby, S. M., Abbott-Brown, D. & Bornstein, P. J. Cell Biol. 95, 351–354 (1982).

  18. 18

    Leech, J. H., Barnwell, J. W., Miller, L. H. & Howard, R. J. J. exp. Med. 159, 1567–1575 (1984).

  19. 19

    Aley, S. B., Sherwood, J. A. & Howard, R. J. J. exp. Med. 160, 1585–1590 (1984).

  20. 20

    Haverstick, D. M., Dixit, V. M., Grant, G. A., Frazier, W. A. & Santoro, S. A. Biochemistry 23, 5597–5603 (1984).

  21. 21

    David, P. H., Hommel, M., Miller, L. H., Udeinya, I. J. & Oligino, L. D. Proc. natn. Acad. Sci. U.S.A. 80, 5075–5079 (1983).

  22. 22

    Degowin, R. L. & Powell, R. D. Am. J. trop. Med. Hyg. 14, 519–528 (1965).

  23. 23

    Collins, W. E., Warren, M., Skinner, J. C., Chin, W. & Richardson, B. B. J. Parasit., 52–56 (1977).

  24. 24

    Graves, P. M., Carter, R., Keystone, J. S. & Seeley, D. C. Jr Am. J. trop. Med. Hyg. 33, 212–219 (1984).

  25. 25

    Trager, W. & Jensen, J. B. Science 193, 673–675 (1976).

  26. 26

    Geiman, Q. M. & Meagher, M. J. Nature 215, 437–439 (1967).

  27. 27

    Barnwell, J. W., Howard, R. J., Coon, H. G. & Miller, L. H. Infect. Immun. 40, 985–994 (1983).

  28. 28

    Haynes, J. D., Diggs, C. L., Hines, F. A. & Desjardins, R. E. Nature 263, 767–769 (1976).

  29. 29

    Sodetz, J. M., Pizzo, S. V. & McKee, P. A. J. biol Chem. 252, 5538–5546 (1977).

  30. 30

    Grinnell, F. & Feld, M. K. J. biol. Chem. 257, 4888–4893 (1982).

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