Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 Oct;64(10):4261–4268. doi: 10.1128/iai.64.10.4261-4268.1996

Plasmodium falciparum gametocyte adhesion to C32 cells via CD36 is inhibited by antibodies to modified band 3.

N J Rogers 1, G A Targett 1, B S Hall 1
PMCID: PMC174366  PMID: 8926098

Abstract

Plasmodium falciparum gametocyte-infected erythrocytes are characterized by their ability to sequester in the microvasculature of various organs, primarily the spleen and bone marrow. This phenomenon is thought to play a critical role in the development and survival of the sexual stages. Little is known, however, about ligands on the gametocyte-infected erythrocyte. Infection of erythrocytes with mature asexual stages of P. falciparum (trophozoites and schizonts) has been shown to induce modification of the erythrocyte anion transporter, band 3, and this has been linked to the acquisition of an adherent phenotype. Here, we demonstrate for the first time that immature gametocyte-infected erythrocytes also express modified band 3. In vitro binding assays demonstrate that gametocyte-infected erythrocytes of the 3D7 strain utilize this surface receptor for adhesion to C32 amelanotic melanoma cells via the host cell receptor CD36 (platelet glycoprotein IIIb). Adhesion of gametocyte-infected erythrocytes to CD36-transfected CHO cells is also dependent on modified band 3. However, modified band 3 does not mediate adhesion of gametocyte-infected erythrocytes to intercellular adhesion molecule 1, a second host receptor for gametocytes expressed on C32 cells.

Full Text

The Full Text of this article is available as a PDF (789.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Asch A. S., Liu I., Briccetti F. M., Barnwell J. W., Kwakye-Berko F., Dokun A., Goldberger J., Pernambuco M. Analysis of CD36 binding domains: ligand specificity controlled by dephosphorylation of an ectodomain. Science. 1993 Nov 26;262(5138):1436–1440. doi: 10.1126/science.7504322. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Barnwell J. W. Cytoadherence and sequestration in falciparum malaria. Exp Parasitol. 1989 Nov;69(4):407–412. doi: 10.1016/0014-4894(89)90190-2. [DOI] [PubMed] [Google Scholar]
  4. Baruch D. I., Gormely J. A., Ma C., Howard R. J., Pasloske B. L. Plasmodium falciparum erythrocyte membrane protein 1 is a parasitized erythrocyte receptor for adherence to CD36, thrombospondin, and intercellular adhesion molecule 1. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3497–3502. doi: 10.1073/pnas.93.8.3497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Berendt A. R., McDowall A., Craig A. G., Bates P. A., Sternberg M. J., Marsh K., Newbold C. I., Hogg N. The binding site on ICAM-1 for Plasmodium falciparum-infected erythrocytes overlaps, but is distinct from, the LFA-1-binding site. Cell. 1992 Jan 10;68(1):71–81. doi: 10.1016/0092-8674(92)90207-s. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Biggs B. A., Anders R. F., Dillon H. E., Davern K. M., Martin M., Petersen C., Brown G. V. Adherence of infected erythrocytes to venular endothelium selects for antigenic variants of Plasmodium falciparum. J Immunol. 1992 Sep 15;149(6):2047–2054. [PubMed] [Google Scholar]
  9. Chulay J. D., Ockenhouse C. F. Host receptors for malaria-infected erythrocytes. Am J Trop Med Hyg. 1990 Aug;43(2 Pt 2):6–14. doi: 10.4269/ajtmh.1990.43.6. [DOI] [PubMed] [Google Scholar]
  10. Crandall I., Collins W. E., Gysin J., Sherman I. W. Synthetic peptides based on motifs present in human band 3 protein inhibit cytoadherence/sequestration of the malaria parasite Plasmodium falciparum. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4703–4707. doi: 10.1073/pnas.90.10.4703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Crandall I., Guthrie N., Sherman I. W. Plasmodium falciparum: sera of individuals living in a malaria-endemic region recognize peptide motifs of the human erythrocyte anion transport protein. Am J Trop Med Hyg. 1995 May;52(5):450–455. doi: 10.4269/ajtmh.1995.52.450. [DOI] [PubMed] [Google Scholar]
  12. Crandall I., Land K. M., Sherman I. W. Plasmodium falciparum: pfalhesin and CD36 form an adhesin/receptor pair that is responsible for the pH-dependent portion of cytoadherence/sequestration. Exp Parasitol. 1994 Mar;78(2):203–209. doi: 10.1006/expr.1994.1020. [DOI] [PubMed] [Google Scholar]
  13. Crandall I., Sherman I. W. Antibodies to synthetic peptides based on band 3 motifs react specifically with Plasmodium falciparum (human malaria)-infected erythrocytes and block cytoadherence. Parasitology. 1994 May;108(Pt 4):389–396. doi: 10.1017/s0031182000075934. [DOI] [PubMed] [Google Scholar]
  14. Crandall I., Sherman I. W. Cytoadherence-related neoantigens on Plasmodium falciparum (human malaria)-infected human erythrocytes result from the exposure of normally cryptic regions of the band 3 protein. Parasitology. 1994 Apr;108(Pt 3):257–267. doi: 10.1017/s0031182000076101. [DOI] [PubMed] [Google Scholar]
  15. Crandall I., Sherman I. W. Plasmodium falciparum (human malaria)-induced modifications in human erythrocyte band 3 protein. Parasitology. 1991 Jun;102(Pt 3):335–340. doi: 10.1017/s0031182000064271. [DOI] [PubMed] [Google Scholar]
  16. Crandall I., Smith H., Sherman I. W. Plasmodium falciparum: the effect of pH and Ca2+ concentration on the in vitro cytoadherence of infected erythrocytes to amelanotic melanoma cells. Exp Parasitol. 1991 Oct;73(3):362–368. doi: 10.1016/0014-4894(91)90108-9. [DOI] [PubMed] [Google Scholar]
  17. Dransfield I., Cabañas C., Craig A., Hogg N. Divalent cation regulation of the function of the leukocyte integrin LFA-1. J Cell Biol. 1992 Jan;116(1):219–226. doi: 10.1083/jcb.116.1.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Guthrie N., Bird D. M., Crandall I., Sherman I. W. Plasmodium falciparum: the adherence of erythrocytes infected with human malaria can be mimicked using pfalhesin-coated microspheres. Cell Adhes Commun. 1995 Dec;3(5):407–417. doi: 10.3109/15419069509081295. [DOI] [PubMed] [Google Scholar]
  20. Guthrie N., Crandall I. E., Marini S., Fasciglione G. F., Sherman I. W. Monoclonal antibodies that react with human band 3 residues 542-555 recognize different conformations of this protein in uninfected and Plasmodium falciparum infected erythrocytes. Mol Cell Biochem. 1995 Mar 23;144(2):117–123. doi: 10.1007/BF00944390. [DOI] [PubMed] [Google Scholar]
  21. Handunnetti S. M., David P. H., Perera K. L., Mendis K. N. Uninfected erythrocytes form "rosettes" around Plasmodium falciparum infected erythrocytes. Am J Trop Med Hyg. 1989 Feb;40(2):115–118. doi: 10.4269/ajtmh.1989.40.115. [DOI] [PubMed] [Google Scholar]
  22. Hasler T., Albrecht G. R., Van Schravendijk M. R., Aguiar J. C., Morehead K. E., Pasloske B. L., Ma C., Barnwell J. W., Greenwood B., Howard R. J. An improved microassay for Plasmodium falciparum cytoadherence using stable transformants of Chinese hamster ovary cells expressing CD36 or intercellular adhesion molecule-1. Am J Trop Med Hyg. 1993 Mar;48(3):332–347. doi: 10.4269/ajtmh.1993.48.332. [DOI] [PubMed] [Google Scholar]
  23. Hogh B., Petersen E., Crandall I., Gottschau A., Sherman I. W. Immune responses to band 3 neoantigens on Plasmodium falciparum-infected erythrocytes in subjects living in an area of intense malaria transmission are associated with low parasite density and high hematocrit value. Infect Immun. 1994 Oct;62(10):4362–4366. doi: 10.1128/iai.62.10.4362-4366.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hommel M. Amplification of cytoadherence in cerebral malaria: towards a more rational explanation of disease pathophysiology. Ann Trop Med Parasitol. 1993 Dec;87(6):627–635. doi: 10.1080/00034983.1993.11812821. [DOI] [PubMed] [Google Scholar]
  25. Iqbal J., Perlmann P., Berzins K. Plasmodium falciparum: analysis of the cytoadherence inhibition of the human monoclonal antibody 33G2 and of antibodies reactive with antigen Pf332. Exp Parasitol. 1993 Aug;77(1):79–87. doi: 10.1006/expr.1993.1063. [DOI] [PubMed] [Google Scholar]
  26. Jensen J. B. Concentration from continuous culture of erythrocytes infected with trophozoites and schizonts of Plasmodium falciparum. Am J Trop Med Hyg. 1978 Nov;27(6):1274–1276. doi: 10.4269/ajtmh.1978.27.1274. [DOI] [PubMed] [Google Scholar]
  27. Kass L., Willerson D., Jr, Rieckmann K. H., Carson P. E., Becker R. P. Plasmodium falciparum gametocytes. Electron microscopic observations on material obtained by a new method. Am J Trop Med Hyg. 1971 Mar;20(2):187–194. [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. Raventos-Suarez C., Kaul D. K., Macaluso F., Nagel R. L. Membrane knobs are required for the microcirculatory obstruction induced by Plasmodium falciparum-infected erythrocytes. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3829–3833. doi: 10.1073/pnas.82.11.3829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Riley E. M., Ong C. S., Olerup O., Eida S., Allen S. J., Bennett S., Andersson G., Targett G. A. Cellular and humoral immune responses to Plasmodium falciparum gametocyte antigens in malaria-immune individuals. Limited response to the 48/45-kilodalton surface antigen does not appear to be due to MHC restriction. J Immunol. 1990 Jun 15;144(12):4810–4816. [PubMed] [Google Scholar]
  32. Ringwald P., Peyron F., Lepers J. P., Rabarison P., Rakotomalala C., Razanamparany M., Rabodonirina M., Roux J., Le Bras J. Parasite virulence factors during falciparum malaria: rosetting, cytoadherence, and modulation of cytoadherence by cytokines. Infect Immun. 1993 Dec;61(12):5198–5204. doi: 10.1128/iai.61.12.5198-5204.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rogers N. J., Daramola O., Targett G. A., Hall B. S. CD36 and intercellular adhesion molecule 1 mediate adhesion of developing Plasmodium falciparum gametocytes. Infect Immun. 1996 Apr;64(4):1480–1483. doi: 10.1128/iai.64.4.1480-1483.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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]
  35. Saul A., Graves P., Edser L. Refractoriness of erythrocytes infected with Plasmodium falciparum gametocytes to lysis by sorbitol. Int J Parasitol. 1990 Dec;20(8):1095–1097. doi: 10.1016/0020-7519(90)90056-s. [DOI] [PubMed] [Google Scholar]
  36. Sein K. K., Maeno Y., Thuc H. V., Anh T. K., Aikawa M. Differential sequestration of parasitized erythrocytes in the cerebrum and cerebellum in human cerebral malaria. Am J Trop Med Hyg. 1993 Apr;48(4):504–511. doi: 10.4269/ajtmh.1993.48.504. [DOI] [PubMed] [Google Scholar]
  37. Sherman I. W., Crandall I. E., Guthrie N., Land K. M. The sticky secrets of sequestration. Parasitol Today. 1995 Oct;11(10):378–384. doi: 10.1016/0169-4758(95)80006-9. [DOI] [PubMed] [Google Scholar]
  38. Sinden R. E. Gametocytogenesis of Plasmodium falciparum in vitro: an electron microscopic study. Parasitology. 1982 Feb;84(1):1–11. doi: 10.1017/s003118200005160x. [DOI] [PubMed] [Google Scholar]
  39. Smalley M. E. Plasmodium falciparum gametocytogenesis in vitro. Nature. 1976 Nov 18;264(5583):271–272. doi: 10.1038/264271a0. [DOI] [PubMed] [Google Scholar]
  40. Smith H., Nelson J. A., Gahmberg C. G., Crandall I., Sherman I. W. Plasmodium falciparum: cytoadherence of malaria-infected erythrocytes to human brain capillary and umbilical vein endothelial cells--a comparative study of adhesive ligands. Exp Parasitol. 1992 Nov;75(3):269–280. doi: 10.1016/0014-4894(92)90212-s. [DOI] [PubMed] [Google Scholar]
  41. 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]
  42. 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]
  43. Tanner M. J., Martin P. G., High S. The complete amino acid sequence of the human erythrocyte membrane anion-transport protein deduced from the cDNA sequence. Biochem J. 1988 Dec 15;256(3):703–712. doi: 10.1042/bj2560703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. 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]
  45. Udeinya I. J., Miller L. H., McGregor I. A., Jensen J. B. Plasmodium falciparum strain-specific antibody blocks binding of infected erythrocytes to amelanotic melanoma cells. Nature. 1983 Jun 2;303(5916):429–431. doi: 10.1038/303429a0. [DOI] [PubMed] [Google Scholar]
  46. Udomsangpetch R., Aikawa M., Berzins K., Wahlgren M., Perlmann P. Cytoadherence of knobless Plasmodium falciparum-infected erythrocytes and its inhibition by a human monoclonal antibody. Nature. 1989 Apr 27;338(6218):763–765. doi: 10.1038/338763a0. [DOI] [PubMed] [Google Scholar]
  47. Wahlgren M., Fernandez V., Scholander C., Carlson J. Rosetting. Parasitol Today. 1994 Feb;10(2):73–79. doi: 10.1016/0169-4758(94)90400-6. [DOI] [PubMed] [Google Scholar]
  48. Wang D. N., Sarabia V. E., Reithmeier R. A., Kühlbrandt W. Three-dimensional map of the dimeric membrane domain of the human erythrocyte anion exchanger, Band 3. EMBO J. 1994 Jul 15;13(14):3230–3235. doi: 10.1002/j.1460-2075.1994.tb06624.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Winograd E., Sherman I. W. Characterization of a modified red cell membrane protein expressed on erythrocytes infected with the human malaria parasite Plasmodium falciparum: possible role as a cytoadherent mediating protein. J Cell Biol. 1989 Jan;108(1):23–30. doi: 10.1083/jcb.108.1.23. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES