Plasmodium falciparum: The behavior of clinical isolates in an in vitro model of infected red blood cell sequestration

Marsh, Kevin; Marsh, Vivienne; Brown, J.; Whittle, Hilton; Greenwood, Brian

doi:10.1016/0014-4894(88)90123-3

Cited by 95 publications

(52 citation statements)

References 11 publications

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“…There is clearly a great diversity of cytoadherence profiles from patient isolates from many places in the world [11][12][13][14][15]23,33 that is explained in part by the variety of different assay systems used. For results to be comparable between settings, standardization of techniques should be encouraged as much as possible.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies found no association between cerebral malaria and parasite adherence, but many have had inadequate sample sizes. [11][12][13][14] In one of these studies, there was an association between adherence to C32 melanoma cells and severe (but not cerebral) malaria in Thai adults. 12 A recent large study from Kenya, using cryopreserved and thawed isolates, showed a trend to more binding to ICAM-1 by isolates from children with cerebral malaria than from children with uncomplicated or asymptomatic disease.…”

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confidence: 99%

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Cytoadherence characteristics of Plasmodium falciparum-infected erythrocytes from Malawian children with severe and uncomplicated malaria.

Rogerson

Tembenu

Dobaño

et al. 1999

The American Journal of Tropical Medicine and Hygiene

135

103

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Abstract. Cytoadherence of Plasmodium falciparum-infected erythrocytes to the microvascular endothelium is believed to be a key factor in the development of cerebral malaria. Erythrocyte rosette formation has been correlated with malaria severity in studies from east and west Africa. We cultured fresh isolates from Malawian children with severe (n ϭ 76) or uncomplicated (n ϭ 79) malaria to pigmented trophozoite stage and examined rosette formation and adherence to CD36, intercellular adhesion molecule-1 (ICAM-1

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Cytoadherence characteristics of Plasmodium falciparum-infected erythrocytes from Malawian children with severe and uncomplicated malaria.

Rogerson

Tembenu

Dobaño

et al. 1999

The American Journal of Tropical Medicine and Hygiene

135

103

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“…Another problem occurs with the predominantly-used cell assays, since there is a pronounced dependency on parasitemia; the linear correlation between parasitemia and cytoadhesion makes the values obtained at low parasitemias difficult to interpret. 27 This, together with the fact that most patients have parasitemias less than 1%, has increased the demand for new techniques.…”

Section: Resultsmentioning

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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“…1) might contain the adhesive region: (i) Cytoadherence is strongly influenced by pH (16,17), consistent with a protonated histidine residue being near to, or part of, the adhesin site. (ii) Cytoadherence is strongly inhibited by the iodination of surface proteins of a P. falciparum-infected erythrocyte (18), implying that a tyrosine residue is near to, or part of, the adhesin site.…”

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confidence: 99%

Synthetic peptides based on motifs present in human band 3 protein inhibit cytoadherence/sequestration of the malaria parasite Plasmodium falciparum.

Crandall

Collins

Gysin

et al. 1993

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

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Synthetic peptides patterned on the amino acid sequences found in two exofacial regions of band 3 protein (residues 824-829 of loop 7 and residues 547-553 of loop 3) blocked, in a dose-dependent fashion, the in vitro adherence of Plasmodium falciparum-infected erythrocytes to C32 amelanotic melanoma cells. Intravenous infusion of these synthetic peptides into Aotus and Saimiri monkeys infected with sequestering isolates of P. fakciparum resulted in the appearance of mature forms of the parasite in the peripheral circulation. The finding that the peptides were effective as adhesion blockers in the micromolar range suggests that cerebral malaria could be managed through antiadhesion therapy.The hallmark ofPlasmodiumfalciparum infections is sequestration-that is, the attachment of erythrocytes infected with mature-stage parasites (trophozoites/schizonts) to the endothelial cells lining the postcapillary venules (1). In humans, the principal organs in which sequestration takes place are the heart, lung, kidney, and liver (2). Sequestration in the brain microvessels-a special pathology of P. falciparum infections called cerebral malaria-may occlude blood flow and result in confusion, lethargy, and deep coma (3). Although the plasmodial molecules on the surface of the malaria-infected erythrocyte that are responsible for binding to the endothelium have not been identified, a parasite-encoded protein, P. falciparum erythrocyte membrane protein 1 (PfEMP 1; ref. 4), similar to a recently described protein called sequestrin (5), has been correlated with cytoadherence. However, the precise role of PfEMP 1 (or sequestrin) in erythrocyte sequestration has not been determined.Earlier work (5-7) indicated that infection of erythrocytes by the malaria parasite P. falciparum leads to truncated forms ofband 3 protein in the erythrocyte membrane and that these were involved in the cytoadherent behavior of the infected erythrocyte. Further, several monoclonal antibodies directed against exofacial loops 3 and 7 of band 3 protein blocked cytoadherence (I.C. and I.W.S., unpublished results). In an attempt to further define the regions of band 3 protein responsible for the cytoadherent behavior of infected erythrocytes, peptides patterned on the surface-exposed domains of band 3 were synthesized, and their ability to inhibit the in vitro and in vivo adherence of P. falciparuminfected erythrocyte was determined.The following observations were used to determine which sequences in the exofacial loops (Fig. 1) might contain the adhesive region: (i) Cytoadherence is strongly influenced by pH (16,17), consistent with a protonated histidine residue being near to, or part of, the adhesin site. (ii) Cytoadherence is strongly inhibited by the iodination of surface proteins of a P. falciparum-infected erythrocyte (18), implying that a tyrosine residue is near to, or part of, the adhesin site. (iii) The adhesin is trypsin sensitive (18), suggesting that a trypsin site (a lysine or arginine) is close to, or part of, the adhesive region. Bec...

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Plasmodium falciparum: The behavior of clinical isolates in an in vitro model of infected red blood cell sequestration

Cited by 95 publications

References 11 publications

Cytoadherence characteristics of Plasmodium falciparum-infected erythrocytes from Malawian children with severe and uncomplicated malaria.

Cytoadherence characteristics of Plasmodium falciparum-infected erythrocytes from Malawian children with severe and uncomplicated malaria.

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

Synthetic peptides based on motifs present in human band 3 protein inhibit cytoadherence/sequestration of the malaria parasite Plasmodium falciparum.

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