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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Aymen M Madkhali
  • Mohammed O Alkurbi
  • Tadge Szestak
  • Anja Bengtsson
  • Pradeep R Patil
  • Yang Wu
  • Saeed Alharthi
  • Jensen, Anja Ramstedt
  • Richard Pleass
  • Alister G Craig

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.

OriginalsprogEngelsk
Artikelnummere111518
TidsskriftPLOS ONE
Vol/bind9
Udgave nummer10
Antal sider8
ISSN1932-6203
DOI
StatusUdgivet - 2014

Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk


Ingen data tilgængelig

ID: 127181656