Human vascular endothelial cell adhesion receptors for plasmoclium falciparum-infected erythrocytes: Roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1

Christian F. Ockenhouse, Tatsuya Tegoshi, Yoshimasa Maeno, Christopher Benjamin, May Ho, Khin Ei Kan, Ye Thway, Kyan Win, Masamichi Aikawa, Roy R. Lobb

Research output: Contribution to journalArticle

308 Citations (Scopus)

Abstract

The clinical complications associated with severe and cerebral malaria occur as a result of the intravascular mechanical obstruction of erythrocytes infected with the asexual stages of the parasite, Plasmodiumfakiparum. We now report that a primary P.fakiparum-infected erythrocyte (parasitized red blood cell [PRBC]) isolate from a patient with severe complicated malaria binds to cytokineinduced human vascular endothelial cells, and that this adhesion is in part mediated by endothelial leukocyte adhesion molecule 1 (ELAM-1) and vascular cell adhesion molecule 1 (VCAM-1). PRBC binding to tumor necrosis factor α (TNF-α-activated human vascular endothelial cells is partially inhibited by antibodies to ELAM-1 and ICAM-1 and the inhibitory effects of these antibodies is additive. PRBCs selected in vitro by sequential panning on purified adhesion molecules bind concurrently to recombinant soluble ELAM-1 and VCAM-1, and to two previously identified endothelial cell receptors for PRBCs, ICAM-1, and CD36. Post-mortem brain tissue from patients who died from cerebral malaria expressed multiple cell adhesion molecules including ELAM-1 and VCAM-1 on cerebral microvascular endothelium not expressed in brains of individuals who died from other causes. These results ascribe novel pathological functions for both ELAM-1 and VCAM-1 and may help delineate alternative adhesion pathways PRBCs use to modify malaria pathology.

Original languageEnglish
Pages (from-to)1183-1189
Number of pages7
JournalJournal of Experimental Medicine
Volume176
Issue number4
DOIs
Publication statusPublished - 01-10-1992

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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