Visualization of Plasmodium falciparum - Endothelium interactions in human microvasculature: Mimicry of leukocyte recruitment

May Ho, Michael J. Hickey, Allan G Murray, Graciela Andonegui, Paul Kubes

Research output: Contribution to journalArticleResearchpeer-review

86 Citations (Scopus)

Abstract

Plasmodium falciparum-infected erythrocytes roll on and/or adhere to CD36, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and P-selectin under shear conditions in vitro. However, the lack of an adequate animal model has made it difficult to determine whether infected erythrocytes do indeed interact in vivo in microvessels. Therefore, we made use of an established model of human skin grafted onto severe combined immunodeficient (SCID) mice to directly visualize the human microvasculature by epifluorescence intravital microscopy. In all grafts examined, infected erythrocytes were observed to roll and/or adhere in not just postcapillary venules but also in arterioles. In contrast, occlusion of capillaries by infected erythrocytes was noted only in approximately half of the experiments. Administration of an anti-CD36 antibody resulted in a rapid reduction of rolling and adhesion. More importantly, already adherent cells quickly detached. The residual rolling after anti-CD36 treatment was largely inhibited by an anti-ICAM-1 antibody. Anti-ICAM-1 alone reduced the ability of infected erythrocytes to sustain rolling and subsequent adhesion. These findings provide conclusive evidence that infected erythrocytes interact within the human microvasculature in vivo by a multistep adhesive cascade that mimics the process of leukocyte recruitment.

Original languageEnglish
Pages (from-to)1205-1211
Number of pages7
JournalJournal of Experimental Medicine
Volume192
Issue number8
DOIs
Publication statusPublished - 16 Oct 2000
Externally publishedYes

Keywords

  • Adhesion molecules
  • Cytoadherence
  • Erythrocytes
  • Malaria
  • Pathogenesis

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