Falciparum Malaria-Infected Erythrocytes Specifically Bind to Cultured Human Endothelial Cells

Udeinya, Iroka J.; Schmidt, John A.; Aikawa, Masamichi; Miller, Louis H.; Green, Ira

doi:10.1126/science.7017935

Cited by 274 publications

(110 citation statements)

References 11 publications

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“…The KAHRP gene product is a component of the knob structure on the surface of parasitized erythrocytes that are responsible for cytoadherence (12,13). Chromosomal breakage events disrupting the KAHRP gene result in parasite mutants that are knobless and cytoadherentdeficient (14,15,16). These mutant parasites possess a growth advantage in cell culture, but are cleared by the host's spleen in vivo (14).…”

Section: Introductionmentioning

confidence: 99%

Chromatin structure determines the sites of chromosome breakages in Plasmodium falciparum

et al. 1994

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Section: Introductionmentioning

confidence: 99%

Chromatin structure determines the sites of chromosome breakages in Plasmodium falciparum

et al. 1994

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“…falciparum lines grown in vitro often rapidly lose the ability to adhere to endothelial cells (8,9). In natural infections this property enables erythrocytes infected with mature parasites to sequester in deep vascular beds, thereby avoiding destruction in the peripheral circulation.…”

mentioning

confidence: 99%

Subtelomeric chromosome deletions in field isolates of Plasmodium falciparum and their relationship to loss of cytoadherence in vitro.

Biggs

Kemp

Brown

1989

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

100

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Subtelomeric deletions are responsible for the loss of expression of several Plasmodium falciparum antigens, including the knob-associated histidine-rich protein (KAHRP). Such deletions are detectable by two-dimensional pulsed-field gradient electrophoresis (PFGE) in which the chromosomes separated in dimension 1 are cleaved with Apa I, and the sizes of telomeric fragments are determined in dimension 2. This sensitive technique has enabled us to examine the role of subtelomeric deletions in two aspects of the biology of Plasmodium falciparum. First, we show that similar subtelomeric deletions to those that occur in vitro also occur in field isolates. Second, we demonstrate a correlation between subtelomeric deletions and loss of the phenotype of "cytoadherence" in cultured isolates. Subclones were generated from the cytoadherent cloned isolate ItG2F6, and their phenotypes were examined with respect to cytoadherence, the expression of "knobs," and agglutination of infected erythrocytes with rabbit antiserum. The only chromosomal change detectable by two-dimensional PFGE among subclones that differ from wild type in each of these three characteristics is a deletion of approximately 100 kilobases at one end of chromosome 2. This deletion includes the gene coding for KAHRP and the subtelomeric repeat designated rep20.Subtelomeric deletions in cultured isolates are known to result in the loss of a number of functional genes of Plasmodium falciparum (1-7). To examine whether this phenomenon occurs in nature or is an artifact of growth in vitro, we used two-dimensional pulsed-field gradient electrophoresis (PFGE) to examine chromosomal DNA from fresh field isolates. This technique allows resolution of telomeric fragments after digestion of separated chromosomes with the restriction endonuclease Apa I. It relies on the observation that a conserved complex consisting of telomeric repeats, an Apa I site(s), and a block of rep20 subtelomeric repeats is common to all chromosomes of P. falciparum (Fig.

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“…One such new antigen is involved in cytoadherence between Plasmodiumfalciparum-infected erythrocytes (IE) 1 and endothelium. IE develop knobs on the erythrocyte surface by which they adhere to venular endothelium in vivo (6) and to human endothelial cells (7) and amelanotic melanoma cells (8) in vitro. Immune serum inhibits cytoadherence of IE to these cells (4).…”

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confidence: 99%

Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum-infected erythrocytes.

Leech¹,

Barnwell²,

Miller³

et al. 1984

The Journal of Experimental Medicine

398

269

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We have identified strain-specific antigens with Camp and St. Lucia strains of P. falciparum of Mr approximately 285,000 and approximately 260,000, respectively. These strain-specific antigens were metabolically labeled with radioactive amino acids, indicating that they were of parasite origin rather than altered host components. These proteins had the properties of a molecule exposed on the surface of infected erythrocytes (IE). First, the proteins are accessible to lactoperoxidase-catalyzed radioiodination of IE. Second, the radioiodinated proteins were cleaved by low concentrations of trypsin (0.1 microgram/ml). Third, these antigens were immunoprecipitated after addition of immune sera to intact IE. Fourth, the strain-specific immuno-precipitation of these proteins correlated with the capacity of immune sera to block cytoadherence of IE in a strain-specific fashion. Fifth, the strain-specific antigen had detergent solubility properties (i.e., insolubility in 1% Triton X-100, solubility in 5% sodium dodecyl sulfate) similar to the variant antigen of P. knowlesi, which has been proven to be a malarial protein exposed on the erythrocyte surface.

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Falciparum Malaria-Infected Erythrocytes Specifically Bind to Cultured Human Endothelial Cells

Cited by 274 publications

References 11 publications

Chromatin structure determines the sites of chromosome breakages in Plasmodium falciparum

Chromatin structure determines the sites of chromosome breakages in Plasmodium falciparum

Subtelomeric chromosome deletions in field isolates of Plasmodium falciparum and their relationship to loss of cytoadherence in vitro.

Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum-infected erythrocytes.

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