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Analyzing the Permeability of the Blood-Brain Barrier by Microbial Traversal through Microvascular Endothelial Cells
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FTY720 restores endothelial cell permeability induced by malaria sera
Karanyaporn Oggungwan1, Supattra Glaharn1, Sumate Ampawong1
1Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand.
Scientific Reports
|July 21, 2018
Summary
Severe malaria increases endothelial cell permeability. FTY720, a sphingosine-1-phosphate analogue, effectively reduced and reversed this increased permeability in vitro, suggesting potential clinical use for protecting against malaria complications.
Area of Science:
- Malariology
- Vascular Biology
- Pharmacology
Background:
- Endothelial cell (EC) hyperpermeability is a hallmark of severe Plasmodium falciparum malaria, leading to critical organ damage.
- Understanding the mechanisms of EC dysfunction in malaria is crucial for developing effective treatments.
Purpose of the Study:
- To investigate EC permeability in response to sera from malaria patients.
- To evaluate the therapeutic potential of FTY720 in restoring EC barrier integrity.
Main Methods:
- Endothelial cells were exposed to sera from patients with Plasmodium vivax, uncomplicated P. falciparum, and complicated P. falciparum malaria.
- Cellular permeability was quantified using a fluorescein isothiocyanate (FITC)-dextran assay.
- The effect of FTY720, a sphingosine-1-phosphate analogue, on EC permeability was assessed.
Main Results:
- Sera from complicated P. falciparum malaria induced significantly higher EC permeability compared to P. vivax and uncomplicated P. falciparum malaria.
- Pre-treatment with FTY720 significantly reduced FITC-dextran leakage in ECs exposed to malaria sera.
- FTY720 demonstrated a rapid and significant reversal of permeability increases caused by complicated P. falciparum sera.
Conclusions:
- FTY720 effectively protects against and reverses malaria-induced endothelial barrier dysfunction in vitro.
- FTY720 shows promise as a therapeutic agent to mitigate severe malaria complications related to EC permeability.
- Further clinical investigation of FTY720 for severe malaria is warranted.
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