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Inhibition of endothelial activation: a new way to treat cerebral malaria?

Publication ,  Journal Article
Wassmer, SC; Cianciolo, GJ; Combes, V; Grau, GE
Published in: PLoS Med
September 2005

BACKGROUND: Malaria is still a major public health problem, partly because the pathogenesis of its major complication, cerebral malaria (CM), remains incompletely understood. However tumor necrosis factor (TNF) is thought to play a key role in the development of this neurological syndrome, as well as lymphotoxin alpha (LT). METHODS AND FINDINGS: Using an in vitro model of CM based on human brain-derived endothelial cells (HBEC-5i), we demonstrate the anti-inflammatory effect of LMP-420, a 2-NH2-6-Cl-9-[(5-dihydroxyboryl)-pentyl] purine that is a transcriptional inhibitor of TNF. When added before or concomitantly to TNF, LMP-420 inhibits endothelial cell (EC) activation, i.e., the up-regulation of both ICAM-1 and VCAM-1 on HBEC-5i surfaces. Subsequently, LMP-420 abolishes the cytoadherence of ICAM-1-specific Plasmodium falciparum-parasitized red blood cells on these EC. Identical but weaker effects are observed when LMP-420 is added with LT. LMP-420 also causes a dramatic reduction of HBEC-5i vesiculation induced by TNF or LT stimulation, as assessed by microparticle release. CONCLUSION: These data provide evidence for a strong in vitro anti-inflammatory effect of LMP-420 and suggest that targeting host cell pathogenic mechanisms might provide a new therapeutic approach to improving the outcome of CM patients.

Duke Scholars

Published In

PLoS Med

DOI

EISSN

1549-1676

Publication Date

September 2005

Volume

2

Issue

9

Start / End Page

e245

Location

United States

Related Subject Headings

  • Vascular Cell Adhesion Molecule-1
  • Tumor Necrosis Factor-alpha
  • Time Factors
  • Purines
  • Purine Nucleosides
  • Plasmodium falciparum
  • Intercellular Adhesion Molecule-1
  • Humans
  • General & Internal Medicine
  • Erythrocytes
 

Citation

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MLA
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Wassmer, S. C., Cianciolo, G. J., Combes, V., & Grau, G. E. (2005). Inhibition of endothelial activation: a new way to treat cerebral malaria? PLoS Med, 2(9), e245. https://doi.org/10.1371/journal.pmed.0020245
Wassmer, Samuel C., George J. Cianciolo, Valéry Combes, and Georges E. Grau. “Inhibition of endothelial activation: a new way to treat cerebral malaria?PLoS Med 2, no. 9 (September 2005): e245. https://doi.org/10.1371/journal.pmed.0020245.
Wassmer SC, Cianciolo GJ, Combes V, Grau GE. Inhibition of endothelial activation: a new way to treat cerebral malaria? PLoS Med. 2005 Sep;2(9):e245.
Wassmer, Samuel C., et al. “Inhibition of endothelial activation: a new way to treat cerebral malaria?PLoS Med, vol. 2, no. 9, Sept. 2005, p. e245. Pubmed, doi:10.1371/journal.pmed.0020245.
Wassmer SC, Cianciolo GJ, Combes V, Grau GE. Inhibition of endothelial activation: a new way to treat cerebral malaria? PLoS Med. 2005 Sep;2(9):e245.

Published In

PLoS Med

DOI

EISSN

1549-1676

Publication Date

September 2005

Volume

2

Issue

9

Start / End Page

e245

Location

United States

Related Subject Headings

  • Vascular Cell Adhesion Molecule-1
  • Tumor Necrosis Factor-alpha
  • Time Factors
  • Purines
  • Purine Nucleosides
  • Plasmodium falciparum
  • Intercellular Adhesion Molecule-1
  • Humans
  • General & Internal Medicine
  • Erythrocytes