title: An analysis of the binding characteristics of a panel of recently selected ICAM-1 binding Plasmodium falciparum patient isolates.
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.
authors.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.
authors.forename: Aymen M
authors.initials: AM
authors.lastname: Madkhali
authors.affiliation: Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Department of Laboratory Medicine, College of Applied Medical Sciences, Umm Al-Qura University, Makkah Al-Mukarramah, Kingdom of Saudi Arabia.
authors.forename: Mohammed O
authors.initials: MO
authors.lastname: Alkurbi
authors.affiliation: Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Tadge
authors.initials: T
authors.lastname: Szestak
authors.affiliation: Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anja
authors.initials: A
authors.lastname: Bengtsson
authors.affiliation: Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Pradeep R
authors.initials: PR
authors.lastname: Patil
authors.affiliation: Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Parasitology, Faculty of Medicine, Umm AL-Qura University, Makkah, Kingdom of Saudia Arabia.
authors.forename: Saeed A
authors.initials: SA
authors.lastname: Al-Harthi
authors.affiliation: Department of Laboratory Medicine, College of Applied Medical Sciences, Umm Al-Qura University, Makkah Al-Mukarramah, Kingdom of Saudi Arabia.
authors.forename: Saeed
authors.initials: S
authors.lastname: Alharthi
authors.affiliation: Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anja T R
authors.initials: AT
authors.lastname: Jensen
authors.affiliation: Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Pleass
authors.affiliation: Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Alister G
authors.initials: AG
authors.lastname: Craig
mesh_terms: D001681:Biological Assay; D002448:Cell Adhesion; D020405:Dermis / Q000098:blood supply / Q000166:cytology; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D010963:Plasmodium falciparum / Q000302:isolation & purification* / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D050505:Mutant Proteins; D018799:Intercellular Adhesion Molecule-1