Articles

Identification and Characterization of the Antigens Expressed On the Surface of Human Erythrocytes Infected With Plasmodium falciparum

Abstract

 

Background: Molecules expressed on the surface of infected erythrocytes (IE) with Plasmodium falci-parum play important roles in malaria pathogenesis and immune evasion. Some of these molecules are specific adhesive ligands mediating adhesion of IE to the vascular endothelium. In the current study, the antigens exposed on the surface of IE with different isolates and various binding subpopulations of P. falciparum were studied.

Methods: A pooled hyper immune serum (HIS) from Malawian adults and eluted antibodies from the surface of the homologous and heterologous parasites were used. The parasite surface molecules were analyzed by Immuno-Gold-Silver enhancement (IGSE) and Western blotting. Mini-column cytoadherence method was used to select various parasite-binding subpopulations.

Results: Surface antigens of all the isolates were recognized by HIS and high recognition of antigens was observed in all isolates with homologous eluted antibodies. Western blot analysis showed that the eluted antibodies reacted with a small subset of antigens compared with HIS. Three bands, PfEMP-1, were detected in the Triton X- insoluble fraction of the ICAM-1 binding subpopulation. Another interesting band was ~ 52-55 kDa in various isolates of P. falciparum. This molecule as de-fined by its low molecular weight, Triton X-100 solubility, surface location and sensitivity to 1 mg/ml trypsin.

Conclusion: The IE's surface antigens differed in parental population compared with the selected subpopulations. These molecules could induce isolate-specific immunity. Antibodies purified from the surface of IE can be used as specific reagents to investigate parasite-derived proteins expressed on the surface of IE.

Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature .2005; 434(7030): 214.

Paulitschke M, Nash GB. Membrane rigidity of red blood cells parasitized by different strains of Plasmodium falciparum. J Lab Clin Med. 1993; 122(5): 581-589.

Smith JD, Chitnis CE, Craig AG et al. Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell. 1995; 82(1): 101-110.

Fernandez V, Hommel M, Chen Q, Hagblom P, Wahlgren M. Small, clonally variant antigens expressed on the surface of the Plasmodium falciparum-infected erythrocyte are encoded by the rif gene family and are the target of human immune responses. J Exp Med. 1999; 190(10): 1393-1404.

Leech JH, Barnwell JW, Miller LH, Howard RJ. Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum-infected erythrocytes. J Exp Med. 1984; 159(6): 1567-1575.

Gardner MJ, Hall N, Fung E et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature. 2002; 419(6906): 498-511.

Roberts DJ, Craig AG, Berendt AR et al. Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature. 1992; 357(6380): 689-692.

Chattopadhyay R, Taneja T, Chakrabarti K, Pillai CR, Chitnis CE. Molecular analysis of the cytoadherence phenotype of a Plasmodium falciparum field isolate that binds intercellular adhesion molecule-1. Mol Biochem Parasitol. 2004; 133(2): 255-265.

Kalantari N, Ghaffari S. Mini-Column for Cy-toadherence: A New Method for Measuring the Relative Size of Binding Subpopulations in Plasmodium falciparum Isolates. Iranian J Parasi-tol. 2011; 6 (4): 8-16.

Jensen ATR, Magistrado P, Sharp S et al. Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes. J Exp Med. 2004; 199(9): 1179.

Newbold C, Warn P, Black G et al. Receptor-specific adhesion and clinical disease in Plasmodium falciparum. Am J Trop Med Hyg. 1997; 57(4): 389-398.

Pasternak ND, Dzikowski R. PfEMP1: an antigen that plays a key role in the pathogenicity and immune evasion of the malaria parasite Plasmodium falciparum. Int J Biochem Cell Biol. 2009; 41(7): 1463-1466.

Rogerson SJ, Tembenu R, Dobano C et al. Cytoadherence characteristics of Plasmodium falciparum-infected erythrocytes from Malawian children with severe and uncomplicated malaria. Am J Trop Med Hyg. 1999; 61(3): 467-472.

Turner GD, Morrison H, Jones M et al. 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; 145(5): 1057-1069.

Gray C, McCormick C, Turner G, Craig A. ICAM-1 can play a major role in mediating P. falciparum adhesion to endothelium under flow. Mol Biochem Parasitol. 2003; 128(2): 187-193.

Fry AE, Auburn S, Diakite M et al. Variation in the ICAM1 gene is not associated with severe malaria phenotypes. Genes Immun. 2008; 9(5): 462-469.

Treutiger CJ, Hedlund I, Helmby H et al. Rosette formation in Plasmodium falciparum isolates and anti-rosette activity of sera from Gambians with cerebral or uncomplicated malaria. Am J Trop Med Hyg. 1992; 46(5): 503-510.

Rowe A, Obeiro J, Newbold CI, Marsh K. Plasmodium falciparum rosetting is associated with malaria severity in Kenya. Infect Immun. 1995(6); 63: 2323-2326.

Carlson J, Helmby H, Hill AV et al. Human cerebral malaria: association with erythrocyte rosetting and lack of anti-rosetting antibodies. Lancet. 1990; 336(8729): 1457-1460.

Cham GK, Turner L, Lusingu J et al. Sequential, ordered acquisition of antibodies to Plasmodium falciparum erythrocyte membrane protein 1 domains. J Immunol. 2009; 183(5): 3356-3363.

Bull PC, Lowe BS, Kortok M et al. Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria. Nat Med. 1998; 4(3): 358-360.

Iqbal J, Perlmann P, Berzins K. Serological diversity of antigens expressed on the surface of erythrocytes infected with Plasmodium falciparum. Trans R Soc Trop Med Hyg. 1993; 87(5): 583-588.

Bull PC, Lowe BS, Kortok M, Marsh K. Antibody recognition of Plasmodium falciparum erythrocyte surface antigens in Kenya: evidence for rare and prevalent variants. Infect Immun. 1999; 67(2): 733-739.

Joergensen L, Turner L, Magistrado P et al. Limited cross-reactivity among domains of the Plasmodium falciparum clone 3D7 erythrocyte membrane protein 1 family. Infect Immun. 2006; 74(12): 6778-6784.

Gamain B, Miller LH, Baruch DI. The surface variant antigens of Plasmodium falciparum contain cross-reactive epitopes. Proc Natl Acad Sci U S A. 2001; 98(5): 2664-2669.

Marsh K, Howard RJ. Antigens induced on erythrocytes by P. falciparum: expression of diverse and conserved determinants. Science. 1986; 231(4734): 150-153.

Mphande F, Bolad A. Culturing of erythrocytic asexual stages of Plasmodium falciparum and P.vivax. In: Moll K, Perlmann H, Scherf A, Wahlgren M, editors. Methods in malaria research. 5ed. 2008. P.1-3. Avaiables from: http://www.mr4.org/Publications/MethodsinMalariaResearch.aspx.

Vogt A. Cultivation of CHO, COS, HUVEC, melanoma, and L cells. In: Moll K, Perlmann H, Scherf A, Wahlgren M, editors. Methods in malaria research. 5ed. 2008. P.41-42. Avaiablesfrom: http://www.mr4.org/Publications/MethodsinMalariaResearch.aspx.

Rekvig OP, Hannestad K. Acid elution of blood group antibodies from intact erythrocytes. Vox Sang. 1977; 33(5): 280-285.

Pasvol G, Wilson RJ, Smalley ME, Brown J. Separation of viable schizont-infected red cells of Plasmodium falciparum from human blood. Ann Trop Med Parasitol. 1978; 72(1): 87-88.

Hommel M, Hughes M, Bond P, Crampton JM. Antibodies and DNA probes used to analyze variant populations of the Indochina-1 strain of Plasmodium falciparum. Infect Immun. 1991; 59(11): 3975-3981.

Hommel M, David PH, Oligino LD. Surface alterations of erythrocytes in Plasmodium falciparum malaria. Antigenic variation, antigenic diversity, and the role of the spleen. J Exp Med. 1983; 157(4): 1137-1148.

Kyes SA, Rowe JA, Kriek N, Newbold CI. Rifins: a second family of clonally variant proteins expressed on the surface of red cells infected with Plasmodium falciparum. Proc Natl Acad Sci U S A. 1999; 96(16): 9333-9338.

le Scanf C, Fandeur T, Morales-Betoulle ME, Mercereau-PuijalonO. Plasmodium falciparum: Altered Expression of Erythrocyte Membrane-Ass-ociated Antigens during Antigenic Variation. Exp Parasitol. 1997; 85(2): 135-148.

Chattopadhyay R, Sharma A, Srivastava VK et al. Plasmodium falciparum infection elicits both variant-specific and cross-reactive antibodies against variant surface antigens. Infect and immun. 2003; 71(2): 597.

Chaiyaroj SC, Coppel RL, Magowan C, Brown GV. A Plasmodium falciparum isolate with a chromosome 9 deletion expresses a trypsin-resistant cytoadherence molecule. Mol Biochem Parasitol. 1994; 67(1): 21-30.

Biggs BA, Anders RF, Dillon HE et al. Adherence of infected erythrocytes to venular endothelium selects for antigenic variants of Plasmodium falciparum. J Immunol. 1992; 149(6): 2047-2054.

Magowan C, Wollish W, Anderson L, Leech J. Cytoadherence by Plasmodium falciparum-in-fected erythrocytes is correlated with the ex-pression of a family of variable proteins on in-fected erythrocytes. J Exp Med. 1988; 168(4): 1307-20.

Gardner J, Pinches R, Roberts D and Newbold C. Variant antigens and endothelial receptor adhesion in Plasmodium falciparum. Proceedings of the National Academy of Sciences. 1996; (8); 93: 3503.

Noviyanti R, Brown GV, Wickham ME et al. Multiple var gene transcripts are expressed in Plasmodium falciparum infected erythrocytes selected for adhesion. Mol Biochem Parasitol. 2001; 114(2): 227-237.

Joergensen L, Bengtsson DC, Bengtsson A et al. Surface co-expression of two different PfEMP1 antigens on single plasmodium falciparum-infected erythrocytes facilitates binding to ICAM1 and PECAM1. PLoS Pathog. 2010; 6(9): e1001083.

Florens L, Liu X, Wang Y et al. Proteomics approach reveals novel proteins on the surface of malaria-infected erythrocytes. Mol Biochem Parasitol. 2004; 135(1): 1-11.

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Keywords
Cytoadherence PfEMP1 Plasmodium falciparum Surface antigens

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Kalantari N, Ghaffari S. Identification and Characterization of the Antigens Expressed On the Surface of Human Erythrocytes Infected With Plasmodium falciparum. Iran J Parasitol. 1;8(2):197-206.