Identification of a Platelet Membrane Glycoprotein as a Falciparum Malaria Sequestration Receptor

Ockenhouse, Christian F.; Tandon, Narendra N.; Magowan, Cathleen; Jamieson, G.A.; Chulay, Jeffrey D.

doi:10.1126/science.2467377

Cited by 286 publications

(149 citation statements)

References 17 publications

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“…These include the adhesion molecules CD36, 7 platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31), 8 intercellular adhesion molecule-1, (ICAM-1), 9 thrombospondin (TSP), 10 and glycosaminoglycan chondroitin sulfate A (CSA). 11 Ex vivo, CD36 is the most frequent target of strains from patients with mild as well as severe P. falciparum malaria, but it is expressed at low levels on the cerebral vasculature.…”

Section: Introductionmentioning

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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Section: Introductionmentioning

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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“…Benzothiophene carboxamide derivatives were checked for their antiparasitic activity against 3D7 (chloroquine sensitive (10). The IC 50 value for growth inhibition of parasite were found to be 1 6 0.3 and 1.18 6 0.2 lM for compounds 6 and 7, respectively ( Table 1).…”

Section: In Vitro Inhibition Of P Falciparum 3d7 Blood-stage Parasitesmentioning

confidence: 99%

“…Sequestration leads to various pathological symptoms such as ataxia, convulsions, hypothermia, and so forth. Mice die of hypothermia within 6-8 days (10,11). Hence, the P. berghei model of malaria in mice constitutes a good model to explore the efficacy of antimalarials.…”

Section: Introductionmentioning

confidence: 99%

Benzothiophene carboxamide derivatives as novel antimalarials

et al. 2011

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SummaryBromo-benzothiophene carboxamide derivatives have been shown in the preceding article to inhibit Plasmodium falciparum Enoyl-ACP reductase. Here, we report bromo-benzothiophene carboxamide derivatives as potent inhibitors of Plasmodium asexual blood-stages in vitro as well as in vivo in the mouse model. These compounds specifically impair the development of metabolically active trophozoite stage of intraerythrocytic cycle and the intravenous administration of 3-bromo-N-(4-fluorobenzyl)-benzo[b]thiophene-2-carboxamide (compound 6) enhances the longevity of P. berghei infected mice by 2 weeks compared to disease control animals thereby preventing the onset of ataxia and convulsions in treated mice. These compounds thus hold promise for the development of potent antimalarials.

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“…Each PfEMP1 is formed from multiple copies of two parasite-specific domain types, the CIDR and DBL domains, which are most often spatially arranged in a linear array (Figure 1) [15]. Different individual domains are capable of interacting with specific human endothelial surface proteins, including endothelial protein C receptor, EPCR [16], intracellular adhesion molecule 1, ICAM-1 [17] and cluster of differentiation 36, CD36 [18].…”

Section: Do Anti-disease Immunogens Have a Place In Future Malaria Vamentioning

confidence: 99%

Towards an anti-disease malaria vaccine

Lennartz

Lavstsen

Higgins

2017

Emerging Topics in Life Sciences

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Human infective parasites, such as those that cause malaria, are highly adapted to evade clearance by the immune system. In situations where they must maintain prolonged interactions with molecules of their host, they often use parasite surface protein families. These families are highly diverse to prevent immune recognition, and yet, to promote parasite survival, their members must retain the ability to interact with specific human receptors. One of the best understood of the parasite surface protein families is the PfEMP1 proteins of Plasmodium falciparum. These molecules cause infected erythrocytes to adhere to human receptors found on blood vessel and tissue surfaces. This protects the parasite within from clearance by the spleen and also causes symptoms of severe malaria. The PfEMP1 are exposed to the immune system during infection and are therefore excellent vaccine candidates for use in an approach to prevent severe disease. A key question, however, is whether their extensive diversity precludes them from forming components of the malaria vaccines of the future?

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Identification of a Platelet Membrane Glycoprotein as a Falciparum Malaria Sequestration Receptor

Cited by 286 publications

References 17 publications

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

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

Benzothiophene carboxamide derivatives as novel antimalarials

Towards an anti-disease malaria vaccine

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