Differential roles of CD36, ICAM-1, and P-selectin in Plasmodium falciparum cytoadherence in vivo

Microcirculation. 2007 Aug;14(6):593-602. doi: 10.1080/10739680701404705.


Cytoadherence of Plasmodium falciparum-infected red blood cells (IRBCs) on human microvascular endothelium is mediated by synergistic adhesive interactions with different adhesion molecules in vitro. Here, the authors used a unique human/severe combined immunodeficient (SCID) mouse chimeric model to directly visualize IRBC-endothelial interactions in an intact human microvasculature in vivo. Stimulation of human skin grafts with 100 ng TNF-alpha for 4 h led to a dramatic reduction in the distance rolled by IRBCs before arrest, so that the majority of IRBCs adhered directly to the endothelium with a 1.8-fold increase in the number of adherent cells. The decrease in rolling distance and increase in adhesion could be reversed by anti-ICAM-1. More importantly, the effect of TNF-alpha could be seen only in the presence of CD36. A further increase in adhesion by 4.9-fold was observed after 24 h of TNF-alpha stimulation. The increase could be reversed by anti-ICAM-1, but not anti-VCAM-1. In histamine-stimulated grafts, the rolling flux fraction and adhesion increased by 2.8- and 1.6-fold, respectively. The increases were attributable to P-selectin as an inhibitory anti-P-selectin antibody abrogated both the increased rolling flux fraction and firm adhesion. These findings indicate that in addition to CD36, ICAM-1, and P-selectin are major contributors to the dynamic process of IRBC adhesion by different mechanisms in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD36 Antigens / physiology*
  • Cell Adhesion*
  • Chimera
  • Endothelium, Vascular / pathology
  • Erythrocytes / parasitology*
  • Erythrocytes / pathology
  • Humans
  • Intercellular Adhesion Molecule-1 / physiology*
  • Mice
  • Microcirculation / parasitology
  • Microcirculation / pathology
  • P-Selectin / physiology*
  • Plasmodium falciparum / pathogenicity*


  • CD36 Antigens
  • P-Selectin
  • Intercellular Adhesion Molecule-1