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The semiconserved head structure of Plasmodium falciparum erythrocyte membrane protein 1 mediates binding to multiple independent host receptors.

Chen Q, Heddini A, Barragan A, Fernandez V, Pearce SF, Wahlgren M - J. Exp. Med. (2000)

Bottom Line: Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature.The NH(2)-terminal head structure (Duffy binding-like domain 1 [DBL1alpha]-cysteine-rich interdomain region [CIDR1alpha]) of a single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here shown to mediate adherence to multiple host receptors including platelet-endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmune immunoglobulin M, three virulence-associated receptor proteins, a heparan sulfate-like glucosaminoglycan, and CD36.DBL2delta was found to mediate additional binding to PECAM-1/CD31.

View Article: PubMed Central - PubMed

Affiliation: Microbiology and Tumor Biology Center, Karolinska Institutet, The Swedish Institute for Infectious Disease Control, S-171 77 Stockholm, Sweden.

ABSTRACT
Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature. Blockage of the blood flow, hampered oxygen delivery, and severe malaria may follow if binding is excessive. The NH(2)-terminal head structure (Duffy binding-like domain 1 [DBL1alpha]-cysteine-rich interdomain region [CIDR1alpha]) of a single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here shown to mediate adherence to multiple host receptors including platelet-endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmune immunoglobulin M, three virulence-associated receptor proteins, a heparan sulfate-like glucosaminoglycan, and CD36. DBL2delta was found to mediate additional binding to PECAM-1/CD31. The exceptional binding activity of the PfEMP1 head structure and its relatively conserved nature argues that it holds an important role in erythrocyte sequestration and therefore in the virulence of the malaria parasite.

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The binding of fluorescence-labeled soluble receptors to the surface of erythrocytes infected with FCR3S1.2. Fluorescence-labeled recombinant human CD36, ICAM-1, or PECAM-1/CD31 was directly incubated with the infected cells. The binding of human nonimmune IgM was detected by incubating the pRBCs with FITC-labeled rabbit anti–human Ig, whereas that of the blood group antigen A was by incubating the infected cells with an A trisaccharide coupled to biotinylated BSA and FITC-avidin. Infected (arrows) and uninfected RBCs are shown with phase–contrast (PC) and in parallel with UV light (UV). The binding shown was at a receptor concentration of 100 μg/ml, and the parasites were counterstained with ethidium bromide. The fluorescence rates were 65–70% (CD36), 0–5% (ICAM-1), 70–80% (PECAM-1/CD31), 75–85% (IgM), and 60–70% (blood group A). For further details, see Materials and Methods.
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Figure 1: The binding of fluorescence-labeled soluble receptors to the surface of erythrocytes infected with FCR3S1.2. Fluorescence-labeled recombinant human CD36, ICAM-1, or PECAM-1/CD31 was directly incubated with the infected cells. The binding of human nonimmune IgM was detected by incubating the pRBCs with FITC-labeled rabbit anti–human Ig, whereas that of the blood group antigen A was by incubating the infected cells with an A trisaccharide coupled to biotinylated BSA and FITC-avidin. Infected (arrows) and uninfected RBCs are shown with phase–contrast (PC) and in parallel with UV light (UV). The binding shown was at a receptor concentration of 100 μg/ml, and the parasites were counterstained with ethidium bromide. The fluorescence rates were 65–70% (CD36), 0–5% (ICAM-1), 70–80% (PECAM-1/CD31), 75–85% (IgM), and 60–70% (blood group A). For further details, see Materials and Methods.

Mentions: To ascertain the adhesive profile of the pRBCs of FCR3S1.2, we studied the binding of various soluble fluorescence-labeled receptors to the live pRBC surface including the blood group A antigen, CD36, PECAM-1/CD31, heparin, and human IgM. Prominent binding of all of the receptor conjugates except soluble ICAM-1–fluorescein was seen to the pRBC surface (Fig. 1; heparin-FITC, not shown). The labeling varied in intensity between the different conjugates: the PECAM-1/CD31 and soluble CD36 fluorescence was the strongest, showing an even distribution all around the pRBC surface (Fig. 1). The adherence of all of the soluble receptors to the pRBCs of a sister clone (FCR3S1.6) 19 that lacks adhesive properties was also studied, but no or very weak binding was seen. These findings confirm the specificity of the assays and the panadhesive profile of this parasite clone, which is also summarized in Table (see also references 7, 11, 13, and 19).


The semiconserved head structure of Plasmodium falciparum erythrocyte membrane protein 1 mediates binding to multiple independent host receptors.

Chen Q, Heddini A, Barragan A, Fernandez V, Pearce SF, Wahlgren M - J. Exp. Med. (2000)

The binding of fluorescence-labeled soluble receptors to the surface of erythrocytes infected with FCR3S1.2. Fluorescence-labeled recombinant human CD36, ICAM-1, or PECAM-1/CD31 was directly incubated with the infected cells. The binding of human nonimmune IgM was detected by incubating the pRBCs with FITC-labeled rabbit anti–human Ig, whereas that of the blood group antigen A was by incubating the infected cells with an A trisaccharide coupled to biotinylated BSA and FITC-avidin. Infected (arrows) and uninfected RBCs are shown with phase–contrast (PC) and in parallel with UV light (UV). The binding shown was at a receptor concentration of 100 μg/ml, and the parasites were counterstained with ethidium bromide. The fluorescence rates were 65–70% (CD36), 0–5% (ICAM-1), 70–80% (PECAM-1/CD31), 75–85% (IgM), and 60–70% (blood group A). For further details, see Materials and Methods.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1887712&req=5

Figure 1: The binding of fluorescence-labeled soluble receptors to the surface of erythrocytes infected with FCR3S1.2. Fluorescence-labeled recombinant human CD36, ICAM-1, or PECAM-1/CD31 was directly incubated with the infected cells. The binding of human nonimmune IgM was detected by incubating the pRBCs with FITC-labeled rabbit anti–human Ig, whereas that of the blood group antigen A was by incubating the infected cells with an A trisaccharide coupled to biotinylated BSA and FITC-avidin. Infected (arrows) and uninfected RBCs are shown with phase–contrast (PC) and in parallel with UV light (UV). The binding shown was at a receptor concentration of 100 μg/ml, and the parasites were counterstained with ethidium bromide. The fluorescence rates were 65–70% (CD36), 0–5% (ICAM-1), 70–80% (PECAM-1/CD31), 75–85% (IgM), and 60–70% (blood group A). For further details, see Materials and Methods.
Mentions: To ascertain the adhesive profile of the pRBCs of FCR3S1.2, we studied the binding of various soluble fluorescence-labeled receptors to the live pRBC surface including the blood group A antigen, CD36, PECAM-1/CD31, heparin, and human IgM. Prominent binding of all of the receptor conjugates except soluble ICAM-1–fluorescein was seen to the pRBC surface (Fig. 1; heparin-FITC, not shown). The labeling varied in intensity between the different conjugates: the PECAM-1/CD31 and soluble CD36 fluorescence was the strongest, showing an even distribution all around the pRBC surface (Fig. 1). The adherence of all of the soluble receptors to the pRBCs of a sister clone (FCR3S1.6) 19 that lacks adhesive properties was also studied, but no or very weak binding was seen. These findings confirm the specificity of the assays and the panadhesive profile of this parasite clone, which is also summarized in Table (see also references 7, 11, 13, and 19).

Bottom Line: Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature.The NH(2)-terminal head structure (Duffy binding-like domain 1 [DBL1alpha]-cysteine-rich interdomain region [CIDR1alpha]) of a single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here shown to mediate adherence to multiple host receptors including platelet-endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmune immunoglobulin M, three virulence-associated receptor proteins, a heparan sulfate-like glucosaminoglycan, and CD36.DBL2delta was found to mediate additional binding to PECAM-1/CD31.

View Article: PubMed Central - PubMed

Affiliation: Microbiology and Tumor Biology Center, Karolinska Institutet, The Swedish Institute for Infectious Disease Control, S-171 77 Stockholm, Sweden.

ABSTRACT
Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature. Blockage of the blood flow, hampered oxygen delivery, and severe malaria may follow if binding is excessive. The NH(2)-terminal head structure (Duffy binding-like domain 1 [DBL1alpha]-cysteine-rich interdomain region [CIDR1alpha]) of a single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here shown to mediate adherence to multiple host receptors including platelet-endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmune immunoglobulin M, three virulence-associated receptor proteins, a heparan sulfate-like glucosaminoglycan, and CD36. DBL2delta was found to mediate additional binding to PECAM-1/CD31. The exceptional binding activity of the PfEMP1 head structure and its relatively conserved nature argues that it holds an important role in erythrocyte sequestration and therefore in the virulence of the malaria parasite.

Show MeSH
Related in: MedlinePlus