Cytoadherence by Plasmodium falciparum-infected erythrocytes is correlated with the expression of a family of variable proteins on infected erythrocytes.

Magowan, Cathleen; Wollish, Wendy S.; Anderson, Linda; Leech, James H.

doi:10.1084/jem.168.4.1307

Cited by 160 publications

(94 citation statements)

References 32 publications

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“…Sequestrin may be a member of a family of high molecular mass antigens (240-400 kDa) on the surface ofP.falciparum-IRBC (15,16). Immunoprecipitation reactions with human and monkey immune sera indicate that this antigen has serologically defined epitopes (15), and cytoadherence by immune sera is inhibited in a strain-specific manner, implying antigenic diversity among parasite strains.…”

Section: Discussionmentioning

confidence: 99%

Sequestrin, a CD36 recognition protein on Plasmodium falciparum malaria-infected erythrocytes identified by anti-idiotype antibodies.

Ockenhouse

Klotz

Tandon

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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The CD36 molecule expressed by human endothelial cells is a receptor for the adhesion of erythrocytes infected with the human malaria parasite Plasmodium falkiparum. A CD36-speciflic monoclonal antibody, OKM8, inhibits the adhesion of malaria-infected erythrocytes (IRBC) to purified CD36 and cells expressing CD36. Monospecific polyconal anti-idiotype (anti-Id) antibodies, raised against monoclonal antibody OKM8, expressed determinants molecularly mimicking the CD36 binding domain for the adhesion of IRBC. Purified rabbit anti-Id antibodies reacted with the surface of IRBC by immunofluorescence, directly supported the adhesion of wild-type P. falciparum malaria isolates, and inhibited IRBC cytoadherence to melanoma cells. An -270-kDa protein was immunoprecipitated by the anti-Id antibodies from surfacelabeled and metabolically labeled IRBC and was competitively inhibited by soluble CD36. These results support the hypothesis that CD36 is a receptor and the =270-kDa protein, sequestrin, is a complementary ligand involved in the adhesion of IRBC to host-cell endothelium. Sequestrin is a candidate malaria vaccine antigen, and anti-Id antibodies that recognize this molecule may be useful for passive immunotherapy of cerebral and severe P. fakiparum malaria.Erythrocytes infected with the human malaria parasite Plasmodiumfalciparum adhere to postcapillary venular endothehum of specific organs and tissues, and the sequestration of infected erythrocytes (IRBC) contributes to the morbidity and mortality of severe and cerebral malaria (1). Cytoadherence of IRBC has been studied in vitro and involves specific receptor/ligand-mediated interactions between one or more IRBC binding ligands and host endothelial receptors CD36 (2-4), thrombospondin (5), and intercellular adhesion molecule 1 (ICAM-1) (6). CD36 appears to be a major surface receptor for the adhesion of IRBC. Purified CD36 binds culture-adapted (3) and naturally acquired wild-type P. falciparum-IRBC (unpublished data). Soluble CD36 inhibits IRBC binding to endothelial cells and melanoma cells bearing surface CD36.The distribution of CD36 in vivo correlates with sequestration of IRBC, and CD36 is expressed by the capillary endothelium of postmortem brain tissue from patients with cerebral malaria (4). The cytoadherence of IRBC to purified CD36 or cells expressing CD36 is inhibited by monoclonal antibodies (mAbs) OKM8 and OKM5 (2, 7). Based on the above observations, we sought to develop an immunologic monospecific probe to define the malaria-IRBC surface molecule mediating cytoadherence. Such an antibody would focus on the ligand specificity of the CD36 receptor as expressed by an anti-idiotype (anti-Id).Anti-Id antibodies raised against the antigen binding sites of antibodies specific for receptors have been used as cellsurface probes to define the molecular interactions between ligands and receptors (8). Some anti-Id antibodies contain the internal image of the receptor (Ab2) and may recognize a complementary receptor-binding site. In this report we descri...

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Section: Discussionmentioning

confidence: 99%

Sequestrin, a CD36 recognition protein on Plasmodium falciparum malaria-infected erythrocytes identified by anti-idiotype antibodies.

Ockenhouse

Klotz

Tandon

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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“…21 These parasite-derived erythrocyte surface antigens are currently thought to mediate mature asexual stage sequestration and clonal antigenic variation. 22 It is likely that all of these properties of P. falciparum infections are mediated by the variable erythrocyte surface antigens, now known as PfEMP-1, 23 encoded by the var genes. [4][5][6] It has also been shown that the immunologic capacity to recognize PfEMP-1 serotypes correlates with age in humans living in areas of high malaria endemicity.…”

Section: Discussionmentioning

confidence: 99%

Seasonal variation in agglutination of Plasmodium falciparum-infected erythrocytes.

Giha¹,

Theander²,

Staalsøe³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. Agglutination and rosette formation are in vitro characteristics of Plasmodium falciparum-infected erythrocytes, which have been associated with host protective immune responses and also with parasite virulence. The present study was carried out in an area of seasonal and unstable malaria transmission in eastern Sudan. Plasma samples were obtained before, during, and after the transmission season from a volunteer cohort of 64 individuals seven years of age and older. These plasmas were assayed for their ability to agglutinate cultured parasitized erythrocytes originally obtained from acute malaria infection samples taken from five of the cohort members. Our data show that the capacity of donor plasma samples to agglutinate parasitized cells depended largely on the time of sampling relative to the transmission season, at least within this epidemiologic setting. Thus, although less than half of the pretransmission season samples could agglutinate any of the five lines of cultured parasites, all post-transmission season samples could agglutinate at least one of the parasite lines, with 74% agglutinating two or more lines. This increase in the agglutination capacity of individual plasma samples after the transmission season occurred essentially regardless of whether an individual had experienced a clinical malaria attack during the transmission season. The study thus confirms the acquisition of agglutinating antibodies following episodes of clinical malaria, but also demonstrates that such acquisition can take place in the absence of disease, presumably as a consequence of subclinical infection. This is the first demonstration of marked seasonal fluctuations in the capacity of individuals' sera to agglutinate parasitized red blood cells. Possible explanations for this effect include a decrease in the levels of agglutinating antibodies between seasons, or shifts in the antigens being recognized by such antibodies from one transmission season to the next. Finally, we showed the existence of marked seasonal fluctuation in the levels of agglutinating antibodies, either because levels of such antibodies are not sustained between seasons or because the antigens recognized change from one season to the next.Erythrocytes infected by Plasmodium falciparum express highly variable parasite-derived neoantigens at the red blood cell surface membrane during the later stages of their development. 1-3 Predominant among these antigens is PfEMP-1, an extremely polymorphic molecule encoded by the recently identified var gene family. [4][5][6] Antibodies responsible for agglutination (cross-linking) of P. falciparum-infected erythrocytes have been shown to specifically recognize variable antigens on the surface membrane of infected erythrocytes, 7, 8 and acquisition of protective immunity has been proposed to reflect the cumulative recognition of such antigens. 9 In line with this hypothesis, the ability of sera to agglutinate parasitized erythrocytes has been shown to correlate with relative protection of the serum donor fro...

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“…Mouse L cells expressing PECAM-1/CD31 and Chinese hamster ovary cells (CHO cells) transfected with CD36 were grown as previously described. 13,19,20 The transfected cells were sorted by fluorescence-activated cell sorting (FACS) to 100% high expression.…”

Section: Methodsmentioning

confidence: 99%

Binding of Plasmodium falciparum-infected erythrocytes to soluble platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31): frequent recognition by clinical isolates.

Heddini

Chen

Obiero

et al. 2001

The American Journal of Tropical Medicine and Hygiene

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Abstract. Platelet-endothelial cell adhesion molecule-1 or CD31 (PECAM-1/CD31) is a receptor recognized by Plasmodium falciparum-parasitized erythrocytes (pRBCs). Fluorescence-labeled soluble recombinant PECAM-1/ CD31 (sPECAM-1/CD31) is shown to bind to the surface of P. falciparum-infected erythrocytes on up to 70% of the cells. Binding is blocked by the addition of the unlabeled receptor in a dose-dependent fashion, but not by unrelated receptor-proteins. A significant correlation was found between the binding of sPECAM-1/CD31 to pRBCs and the binding to transfected L cells expressing the receptor as seen with six different P. falciparum lines or clones. Panning of cultures on PECAM-1/CD31 transfected L cells was paralleled by an increase in the binding of sPECAM-1/CD31. The pRBCs of 54% of fresh patient-isolates bound sPECAM-1/CD31 with a mean rate of 12.9% (range ϭ 1.1-44%). The data suggest that PECAM-1/CD31 is a common receptor recognized by wild isolates and that the soluble PECAM-1/CD31 suspension assay is a sensitive and reliable way to study PECAM-1/CD31 binding.

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Cytoadherence by Plasmodium falciparum-infected erythrocytes is correlated with the expression of a family of variable proteins on infected erythrocytes.

Cited by 160 publications

References 32 publications

Sequestrin, a CD36 recognition protein on Plasmodium falciparum malaria-infected erythrocytes identified by anti-idiotype antibodies.

Sequestrin, a CD36 recognition protein on Plasmodium falciparum malaria-infected erythrocytes identified by anti-idiotype antibodies.

Seasonal variation in agglutination of Plasmodium falciparum-infected erythrocytes.

Binding of Plasmodium falciparum-infected erythrocytes to soluble platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31): frequent recognition by clinical isolates.

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