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Selection of Plasmodium falciparum Parasites for Cytoadhesion to Human Brain Endothelial Cells
10:09

Selection of Plasmodium falciparum Parasites for Cytoadhesion to Human Brain Endothelial Cells

Published on: January 3, 2012

Plasmodium falciparum-infected erythrocytes decrease the integrity of human blood-brain barrier endothelial cell

Abhai K Tripathi1, David J Sullivan, Monique F Stins

  • 1W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.

The Journal of Infectious Diseases
|March 3, 2007
PubMed
Abstract

Insights

Plasmodium falciparum-infected red blood cells (Pf-IRBCs) disrupt the blood-brain barrier (BBB) integrity in cerebral malaria. Both membrane and soluble Pf-IRBC factors contribute to this BBB dysfunction.

Area of Science:

  • Neuroscience
  • Infectious Disease Research
  • Cell Biology

Background:

  • Cerebral malaria (CM) pathogenesis involves Plasmodium falciparum-infected red blood cells (Pf-IRBCs) sequestering at the blood-brain barrier (BBB).
  • Molecular mechanisms linking Pf-IRBCs to BBB dysfunction remain poorly understood.

Purpose of the Study:

  • To investigate how Pf-IRBCs affect the integrity of the human BBB.
  • To identify Pf-IRBC components responsible for BBB disruption.

Main Methods:

  • Utilized an in vitro human BBB model with electrical cell substrate sensing and transendothelial electrical resistance measurements.
  • Subfractionated Pf-IRBCs and treated them with trypsin, artemisinin, or brefeldin A.

Main Results:

  • Pf-IRBCs significantly reduced BBB electrical resistance, unlike normal red blood cells.
  • Both membrane-associated and soluble Pf-IRBC factors were found to decrease BBB resistance.
  • Trypsin treatment reduced Pf-IRBC binding but not their effect on resistance; soluble factors caused a 50%-70% resistance decrease.

Conclusions:

  • Trypsin-resistant membrane components and soluble factors from Pf-IRBCs contribute to impaired BBB integrity in CM.
  • Pf-IRBCs impact BBB integrity through a multistep, multifactorial process.

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