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. 1997 Nov 15;100(10):2521–2529. doi: 10.1172/JCI119794

Intercellular adhesion molecule-1 and CD36 synergize to mediate adherence of Plasmodium falciparum-infected erythrocytes to cultured human microvascular endothelial cells.

C J McCormick 1, A Craig 1, D Roberts 1, C I Newbold 1, A R Berendt 1
PMCID: PMC508452  PMID: 9366566

Abstract

We have compared the adhesion of Plasmodium falciparum-infected erythrocytes to human dermal microvascular endothelial cells (HDMEC) and human umbilical vein endothelial cells (HUVEC) and have assessed the relative roles of the receptors CD36 and intercellular adhesion molecule-1 (ICAM-1). HUVEC (a cell line that expresses high levels of ICAM-1 but no CD36) mediate low levels of adhesion, whereas HDMEC (which constitutively express CD36) mediate high levels of adhesion even before ICAM-1 induction ICAM-1 expression leads to yet greater levels of adhesion, which are inhibited both by anti-ICAM-1 and CD36 mAbs, despite no increase in the expression of CD36. The results indicate the presence of a substantial population of infected cells that require the presence of both receptors to establish adhesion. Synergy between these receptors could be demonstrated using a number of parasite lines, but it could not be predicted from the binding of these same parasite lines to purified ICAM-1 and CD36. This phenomenon could not be reproduced using either purified receptors presented on plastic, or formalin-fixed HDMEC, suggesting that receptor mobility is important. This is the first study to demonstrate receptor synergy in malaria cytoadherence to human endothelial cells, a phenomenon necessary for parasite survival and associated with disease severity.

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Selected References

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  1. Barnwell J. W., Asch A. S., Nachman R. L., Yamaya M., Aikawa M., Ingravallo P. A human 88-kD membrane glycoprotein (CD36) functions in vitro as a receptor for a cytoadherence ligand on Plasmodium falciparum-infected erythrocytes. J Clin Invest. 1989 Sep;84(3):765–772. doi: 10.1172/JCI114234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnwell J. W., Ockenhouse C. F., Knowles D. M., 2nd Monoclonal antibody OKM5 inhibits the in vitro binding of Plasmodium falciparum-infected erythrocytes to monocytes, endothelial, and C32 melanoma cells. J Immunol. 1985 Nov;135(5):3494–3497. [PubMed] [Google Scholar]
  3. Baruch D. I., Pasloske B. L., Singh H. B., Bi X., Ma X. C., Feldman M., Taraschi T. F., Howard R. J. Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell. 1995 Jul 14;82(1):77–87. doi: 10.1016/0092-8674(95)90054-3. [DOI] [PubMed] [Google Scholar]
  4. Berendt A. R., Simmons D. L., Tansey J., Newbold C. I., Marsh K. Intercellular adhesion molecule-1 is an endothelial cell adhesion receptor for Plasmodium falciparum. Nature. 1989 Sep 7;341(6237):57–59. doi: 10.1038/341057a0. [DOI] [PubMed] [Google Scholar]
  5. Cooke B. M., Berendt A. R., Craig A. G., MacGregor J., Newbold C. I., Nash G. B. Rolling and stationary cytoadhesion of red blood cells parasitized by Plasmodium falciparum: separate roles for ICAM-1, CD36 and thrombospondin. Br J Haematol. 1994 May;87(1):162–170. doi: 10.1111/j.1365-2141.1994.tb04887.x. [DOI] [PubMed] [Google Scholar]
  6. Davison P. M., Bensch K., Karasek M. A. Isolation and growth of endothelial cells from the microvessels of the newborn human foreskin in cell culture. J Invest Dermatol. 1980 Oct;75(4):316–321. doi: 10.1111/1523-1747.ep12530941. [DOI] [PubMed] [Google Scholar]
  7. Duperray A., Languino L. R., Plescia J., McDowall A., Hogg N., Craig A. G., Berendt A. R., Altieri D. C. Molecular identification of a novel fibrinogen binding site on the first domain of ICAM-1 regulating leukocyte-endothelium bridging. J Biol Chem. 1997 Jan 3;272(1):435–441. doi: 10.1074/jbc.272.1.435. [DOI] [PubMed] [Google Scholar]
  8. Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
  9. Fried M., Duffy P. E. Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science. 1996 Jun 7;272(5267):1502–1504. doi: 10.1126/science.272.5267.1502. [DOI] [PubMed] [Google Scholar]
  10. Gardner J. P., Pinches R. A., Roberts D. J., Newbold C. I. Variant antigens and endothelial receptor adhesion in Plasmodium falciparum. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3503–3508. doi: 10.1073/pnas.93.8.3503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hasler T., Handunnetti S. M., Aguiar J. C., van Schravendijk M. R., Greenwood B. M., Lallinger G., Cegielski P., Howard R. J. In vitro rosetting, cytoadherence, and microagglutination properties of Plasmodium falciparum-infected erythrocytes from Gambian and Tanzanian patients. Blood. 1990 Nov 1;76(9):1845–1852. [PubMed] [Google Scholar]
  12. Imcke E., Ruszczak Z., Mayer-da Silva A., Detmar M., Orfanos C. E. Cultivation of human dermal microvascular endothelial cells in vitro: immunocytochemical and ultrastructural characterization and effect of treatment with three synthetic retinoids. Arch Dermatol Res. 1991;283(3):149–157. doi: 10.1007/BF00372054. [DOI] [PubMed] [Google Scholar]
  13. Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Johnson J. K., Swerlick R. A., Grady K. K., Millet P., Wick T. M. Cytoadherence of Plasmodium falciparum-infected erythrocytes to microvascular endothelium is regulatable by cytokines and phorbol ester. J Infect Dis. 1993 Mar;167(3):698–703. doi: 10.1093/infdis/167.3.698. [DOI] [PubMed] [Google Scholar]
  15. Ketis N. V., Lawler J., Hoover R. L., Karnovsky M. J. Effects of heat shock on the expression of thrombospondin by endothelial cells in culture. J Cell Biol. 1988 Mar;106(3):893–904. doi: 10.1083/jcb.106.3.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kuzu I., Bicknell R., Harris A. L., Jones M., Gatter K. C., Mason D. Y. Heterogeneity of vascular endothelial cells with relevance to diagnosis of vascular tumours. J Clin Pathol. 1992 Feb;45(2):143–148. doi: 10.1136/jcp.45.2.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Languino L. R., Plescia J., Duperray A., Brian A. A., Plow E. F., Geltosky J. E., Altieri D. C. Fibrinogen mediates leukocyte adhesion to vascular endothelium through an ICAM-1-dependent pathway. Cell. 1993 Jul 2;73(7):1423–1434. doi: 10.1016/0092-8674(93)90367-y. [DOI] [PubMed] [Google Scholar]
  18. Lawrence M. B., Springer T. A. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991 May 31;65(5):859–873. doi: 10.1016/0092-8674(91)90393-d. [DOI] [PubMed] [Google Scholar]
  19. MacPherson G. G., Warrell M. J., White N. J., Looareesuwan S., Warrell D. A. Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol. 1985 Jun;119(3):385–401. [PMC free article] [PubMed] [Google Scholar]
  20. Marks R. M., Czerniecki M., Penny R. Human dermal microvascular endothelial cells: an improved method for tissue culture and a description of some singular properties in culture. In Vitro Cell Dev Biol. 1985 Nov;21(11):627–635. doi: 10.1007/BF02623295. [DOI] [PubMed] [Google Scholar]
  21. Marsh K., Marsh V. M., Brown J., Whittle H. C., Greenwood B. M. Plasmodium falciparum: the behavior of clinical isolates in an in vitro model of infected red blood cell sequestration. Exp Parasitol. 1988 Apr;65(2):202–208. doi: 10.1016/0014-4894(88)90123-3. [DOI] [PubMed] [Google Scholar]
  22. Ockenhouse C. F., Ho M., Tandon N. N., Van Seventer G. A., Shaw S., White N. J., Jamieson G. A., Chulay J. D., Webster H. K. Molecular basis of sequestration in severe and uncomplicated Plasmodium falciparum malaria: differential adhesion of infected erythrocytes to CD36 and ICAM-1. J Infect Dis. 1991 Jul;164(1):163–169. doi: 10.1093/infdis/164.1.163. [DOI] [PubMed] [Google Scholar]
  23. Ockenhouse C. F., Tandon N. N., Magowan C., Jamieson G. A., Chulay J. D. Identification of a platelet membrane glycoprotein as a falciparum malaria sequestration receptor. Science. 1989 Mar 17;243(4897):1469–1471. doi: 10.1126/science.2467377. [DOI] [PubMed] [Google Scholar]
  24. Ockenhouse C. F., Tegoshi T., Maeno Y., Benjamin C., Ho M., Kan K. E., Thway Y., Win K., Aikawa M., Lobb R. R. Human vascular endothelial cell adhesion receptors for Plasmodium falciparum-infected erythrocytes: roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1. J Exp Med. 1992 Oct 1;176(4):1183–1189. doi: 10.1084/jem.176.4.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Oquendo P., Hundt E., Lawler J., Seed B. CD36 directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes. Cell. 1989 Jul 14;58(1):95–101. doi: 10.1016/0092-8674(89)90406-6. [DOI] [PubMed] [Google Scholar]
  26. Pober J. S., Gimbrone M. A., Jr, Lapierre L. A., Mendrick D. L., Fiers W., Rothlein R., Springer T. A. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed] [Google Scholar]
  27. Pongponratn E., Riganti M., Punpoowong B., Aikawa M. Microvascular sequestration of parasitized erythrocytes in human falciparum malaria: a pathological study. Am J Trop Med Hyg. 1991 Feb;44(2):168–175. doi: 10.4269/ajtmh.1991.44.168. [DOI] [PubMed] [Google Scholar]
  28. Roberts D. D., Sherwood J. A., Spitalnik S. L., Panton L. J., Howard R. J., Dixit V. M., Frazier W. A., Miller L. H., Ginsburg V. Thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence. Nature. 1985 Nov 7;318(6041):64–66. doi: 10.1038/318064a0. [DOI] [PubMed] [Google Scholar]
  29. Roberts D. J., Craig A. G., Berendt A. R., Pinches R., Nash G., Marsh K., Newbold C. I. Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature. 1992 Jun 25;357(6380):689–692. doi: 10.1038/357689a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rogerson S. J., Chaiyaroj S. C., Ng K., Reeder J. C., Brown G. V. Chondroitin sulfate A is a cell surface receptor for Plasmodium falciparum-infected erythrocytes. J Exp Med. 1995 Jul 1;182(1):15–20. doi: 10.1084/jem.182.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Savill J., Hogg N., Ren Y., Haslett C. Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis. J Clin Invest. 1992 Oct;90(4):1513–1522. doi: 10.1172/JCI116019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schmidt J. A., Udeinya I. J., Leech J. H., Hay R. J., Aikawa M., Barnwell J., Green I., Miller L. H. Plasmodium falciparum malaria. An amelanotic melanoma cell line bears receptors for the knob ligand on infected erythrocytes. J Clin Invest. 1982 Aug;70(2):379–386. doi: 10.1172/JCI110627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sherwood J. A., Roberts D. D., Marsh K., Harvey E. B., Spitalnik S. L., Miller L. H., Howard R. J. Thrombospondin binding by parasitized erythrocyte isolates in falciparum malaria. Am J Trop Med Hyg. 1987 Mar;36(2):228–233. doi: 10.4269/ajtmh.1987.36.228. [DOI] [PubMed] [Google Scholar]
  34. Smith J. D., Chitnis C. E., Craig A. G., Roberts D. J., Hudson-Taylor D. E., Peterson D. S., Pinches R., Newbold C. I., Miller L. H. Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell. 1995 Jul 14;82(1):101–110. doi: 10.1016/0092-8674(95)90056-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Su X. Z., Heatwole V. M., Wertheimer S. P., Guinet F., Herrfeldt J. A., Peterson D. S., Ravetch J. A., Wellems T. E. The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell. 1995 Jul 14;82(1):89–100. doi: 10.1016/0092-8674(95)90055-1. [DOI] [PubMed] [Google Scholar]
  36. Swerlick R. A., Garcia-Gonzalez E., Kubota Y., Xu Y. L., Lawley T. J. Studies of the modulation of MHC antigen and cell adhesion molecule expression on human dermal microvascular endothelial cells. J Invest Dermatol. 1991 Aug;97(2):190–196. doi: 10.1111/1523-1747.ep12479643. [DOI] [PubMed] [Google Scholar]
  37. Swerlick R. A., Lee K. H., Wick T. M., Lawley T. J. Human dermal microvascular endothelial but not human umbilical vein endothelial cells express CD36 in vivo and in vitro. J Immunol. 1992 Jan 1;148(1):78–83. [PubMed] [Google Scholar]
  38. Tandon N. N., Lipsky R. H., Burgess W. H., Jamieson G. A. Isolation and characterization of platelet glycoprotein IV (CD36). J Biol Chem. 1989 May 5;264(13):7570–7575. [PubMed] [Google Scholar]
  39. Trager W., Jensen J. B. Human malaria parasites in continuous culture. Science. 1976 Aug 20;193(4254):673–675. doi: 10.1126/science.781840. [DOI] [PubMed] [Google Scholar]
  40. Turner G. D., Morrison H., Jones M., Davis T. M., Looareesuwan S., Buley I. D., Gatter K. C., Newbold C. I., Pukritayakamee S., Nagachinta B. An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol. 1994 Nov;145(5):1057–1069. [PMC free article] [PubMed] [Google Scholar]
  41. Udeinya I. J., Schmidt J. A., Aikawa M., Miller L. H., Green I. Falciparum malaria-infected erythrocytes specifically bind to cultured human endothelial cells. Science. 1981 Jul 31;213(4507):555–557. doi: 10.1126/science.7017935. [DOI] [PubMed] [Google Scholar]
  42. Wellicome S. M., Thornhill M. H., Pitzalis C., Thomas D. S., Lanchbury J. S., Panayi G. S., Haskard D. O. A monoclonal antibody that detects a novel antigen on endothelial cells that is induced by tumor necrosis factor, IL-1, or lipopolysaccharide. J Immunol. 1990 Apr 1;144(7):2558–2565. [PubMed] [Google Scholar]

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