Intercellular adhesion molecule-1 and CD36 synergize to mediate adherence of Plasmodium falciparum-infected erythrocytes to cultured human microvascular endothelial cells

Christopher J. McCormick, Alister Craig, David Roberts, Christopher I. Newbold, Anthony R. Berendt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

125 Citations (Scopus)

Abstract

We have compared the adhesion of Plasmodium falciparum-infected erythrocytes to human dermal microvascular endothelial cells (HDMEC) and human umbilical vein endothelial cells (HUVEC) and have assessed the relative roles of the receptors CD36 and intercellular adhesion molecule-1 (ICAM-1). HUVEC (a cell line that expresses high levels of ICAM-1 but no CD36) mediate low levels of adhesion, whereas HDMEC (which constitutively express CD36) mediate high levels of adhesion even before ICAM-1 induction. ICAM-1 expression leads to yet greater levels of adhesion, which are inhibited both by anti-ICAM-1 and CD36 mAbs, despite no increase in the expression of CD36. The results indicate the presence of a substantial population of infected cells that require the presence of both receptors to establish adhesion. Synergy between these receptors could be demonstrated using a number of parasite lines, but it could not be predicted from the binding of these same parasite lines to purified ICAM-1 and CD36. This phenomenon could not be reproduced using either purified receptors presented on plastic, or formalin- fixed HDMEC, suggesting that receptor mobility is important. This is the first study to demonstrate receptor synergy in malaria cytoadherence to human endothelial cells, a phenomenon necessary for parasite survival and associated with disease severity.

Original languageEnglish
Pages (from-to)2521-2529
Number of pages9
JournalJournal of Clinical Investigation
Volume100
Issue number10
DOIs
Publication statusPublished - 15 Nov 1997
Externally publishedYes

Keywords

  • Cytoadherence
  • Intercellular adhesion molecule- 1
  • Malaria
  • Pathogenesis
  • Receptor

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