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An analysis of the binding characteristics of a panel of recently selected ICAM-1 binding Plasmodium falciparum patient isolates.

Madkhali AM, Alkurbi MO, Szestak T, Bengtsson A, Patil PR, Wu Y, Alharthi S, Jensen AT, Pleass R, Craig AG - PLoS ONE (2014)

Bottom Line: One of the commonly used host receptors is ICAM-1, and it has been suggested that ICAM-1 has a role in cerebral malaria pathology, although the evidence to support this is not conclusive.We also characterised the binding phenotypes using Human Dermal Microvascular Endothelial Cells (HDMEC) under flow conditions.The results show that different isolates have variant-specific binding phenotypes under both static and flow conditions, extending our previous observations that this variation might be due to variable contact residues on ICAM-1 being used by different parasite PfEMP1 variants.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Kingdom of Saudi Arabia.

ABSTRACT
The basis of severe malaria pathogenesis in part includes sequestration of Plasmodium falciparum-infected erythrocytes (IE) from the peripheral circulation. This phenomenon is mediated by the interaction between several endothelial receptors and one of the main parasite-derived variant antigens (PfEMP1) expressed on the surface of the infected erythrocyte membrane. One of the commonly used host receptors is ICAM-1, and it has been suggested that ICAM-1 has a role in cerebral malaria pathology, although the evidence to support this is not conclusive. The current study examined the cytoadherence patterns of lab-adapted patient isolates after selecting on ICAM-1. We investigated the binding phenotypes using variant ICAM-1 proteins including ICAM-1Ref, ICAM-1Kilifi, ICAM-1S22/A, ICAM-1L42/A and ICAM-1L44/A using static assays. The study also examined ICAM-1 blocking by four anti-ICAM-1 monoclonal antibodies (mAb) under static conditions. We also characterised the binding phenotypes using Human Dermal Microvascular Endothelial Cells (HDMEC) under flow conditions. The results show that different isolates have variant-specific binding phenotypes under both static and flow conditions, extending our previous observations that this variation might be due to variable contact residues on ICAM-1 being used by different parasite PfEMP1 variants.

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Static adhesion assay.The same method as for Fig. 1 but with the addition of 5 µg/ml ofmAbs 15.2 (A), My13 (B), 8.46A (C) and BBIG-I1 (D) prior the IE incubation with ICAM-1Ref. The results show the percentage of binding in the presence of ICAM-1 mAb compared to the no mAb treatment (A), and the bars represents SE (n>3).
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pone-0111518-g002: Static adhesion assay.The same method as for Fig. 1 but with the addition of 5 µg/ml ofmAbs 15.2 (A), My13 (B), 8.46A (C) and BBIG-I1 (D) prior the IE incubation with ICAM-1Ref. The results show the percentage of binding in the presence of ICAM-1 mAb compared to the no mAb treatment (A), and the bars represents SE (n>3).

Mentions: The effect of anti-ICAM-1 mAbs on the binding of IE to purified ICAM-1 under static conditions has been studied using specific mAbs reacting with epitopes on Ig-like domains 1 and 2. MAbs 15.2, BBIG-I1 and My13 mapping to domain 1, and 8.4A6 mAb mapping to domain 2 were used in a study that differentiated between the binding sites on ICAM-1 for IE and LFA-1 [13]. Figure 2 (and Data S2) show that different mAbs have different inhibitory effects on the isolates. The results are expressed as the percentage of the binding of each isolate against its binding to ICAM-1Ref. The binding of most of the isolates was reduced by about 75% by two mAbs 15.2 and My13. However, there was only 40% inhibition caused by 15.2 and My13 to PO69 (Figure 2A–B). The inhibition caused by 8.4A6 was different. The effect varied between 25–50% for most of the isolates, although there was no effect by 8.4A6 on the ItG and 8206 isolates (Figure 2C). The range of inhibition for BBIG-I1 was between 25%–75% for nearly all isolates except there was almost no effect on 8206 (Figure 2D). These variations again suggest the use of variable contact residues between ICAM-1 and variant PfEMP-1 proteins.


An analysis of the binding characteristics of a panel of recently selected ICAM-1 binding Plasmodium falciparum patient isolates.

Madkhali AM, Alkurbi MO, Szestak T, Bengtsson A, Patil PR, Wu Y, Alharthi S, Jensen AT, Pleass R, Craig AG - PLoS ONE (2014)

Static adhesion assay.The same method as for Fig. 1 but with the addition of 5 µg/ml ofmAbs 15.2 (A), My13 (B), 8.46A (C) and BBIG-I1 (D) prior the IE incubation with ICAM-1Ref. The results show the percentage of binding in the presence of ICAM-1 mAb compared to the no mAb treatment (A), and the bars represents SE (n>3).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4216080&req=5

pone-0111518-g002: Static adhesion assay.The same method as for Fig. 1 but with the addition of 5 µg/ml ofmAbs 15.2 (A), My13 (B), 8.46A (C) and BBIG-I1 (D) prior the IE incubation with ICAM-1Ref. The results show the percentage of binding in the presence of ICAM-1 mAb compared to the no mAb treatment (A), and the bars represents SE (n>3).
Mentions: The effect of anti-ICAM-1 mAbs on the binding of IE to purified ICAM-1 under static conditions has been studied using specific mAbs reacting with epitopes on Ig-like domains 1 and 2. MAbs 15.2, BBIG-I1 and My13 mapping to domain 1, and 8.4A6 mAb mapping to domain 2 were used in a study that differentiated between the binding sites on ICAM-1 for IE and LFA-1 [13]. Figure 2 (and Data S2) show that different mAbs have different inhibitory effects on the isolates. The results are expressed as the percentage of the binding of each isolate against its binding to ICAM-1Ref. The binding of most of the isolates was reduced by about 75% by two mAbs 15.2 and My13. However, there was only 40% inhibition caused by 15.2 and My13 to PO69 (Figure 2A–B). The inhibition caused by 8.4A6 was different. The effect varied between 25–50% for most of the isolates, although there was no effect by 8.4A6 on the ItG and 8206 isolates (Figure 2C). The range of inhibition for BBIG-I1 was between 25%–75% for nearly all isolates except there was almost no effect on 8206 (Figure 2D). These variations again suggest the use of variable contact residues between ICAM-1 and variant PfEMP-1 proteins.

Bottom Line: One of the commonly used host receptors is ICAM-1, and it has been suggested that ICAM-1 has a role in cerebral malaria pathology, although the evidence to support this is not conclusive.We also characterised the binding phenotypes using Human Dermal Microvascular Endothelial Cells (HDMEC) under flow conditions.The results show that different isolates have variant-specific binding phenotypes under both static and flow conditions, extending our previous observations that this variation might be due to variable contact residues on ICAM-1 being used by different parasite PfEMP1 variants.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Kingdom of Saudi Arabia.

ABSTRACT
The basis of severe malaria pathogenesis in part includes sequestration of Plasmodium falciparum-infected erythrocytes (IE) from the peripheral circulation. This phenomenon is mediated by the interaction between several endothelial receptors and one of the main parasite-derived variant antigens (PfEMP1) expressed on the surface of the infected erythrocyte membrane. One of the commonly used host receptors is ICAM-1, and it has been suggested that ICAM-1 has a role in cerebral malaria pathology, although the evidence to support this is not conclusive. The current study examined the cytoadherence patterns of lab-adapted patient isolates after selecting on ICAM-1. We investigated the binding phenotypes using variant ICAM-1 proteins including ICAM-1Ref, ICAM-1Kilifi, ICAM-1S22/A, ICAM-1L42/A and ICAM-1L44/A using static assays. The study also examined ICAM-1 blocking by four anti-ICAM-1 monoclonal antibodies (mAb) under static conditions. We also characterised the binding phenotypes using Human Dermal Microvascular Endothelial Cells (HDMEC) under flow conditions. The results show that different isolates have variant-specific binding phenotypes under both static and flow conditions, extending our previous observations that this variation might be due to variable contact residues on ICAM-1 being used by different parasite PfEMP1 variants.

Show MeSH
Related in: MedlinePlus