title: Host vascular endothelial growth factor is trophic for Plasmodium falciparum-infected red blood cells.
abstract: Plasmodium falciparum, the protozoan parasite responsible for severe malaria infection, undergoes a complex life cycle. Infected red blood cells (iRBC) sequester in host cerebral microvessels, which underlies the pathology of cerebral malaria. Using immunohistochemistry on post mortem brain samples, we demonstrated positive staining for vascular endothelial growth factor (VEGF) on iRBC. Confocal microscopy of cultured iRBC revealed accumulation of VEGF within the parasitophorous vacuole, expression of host VEGF-receptor 1 and activated VEGF-receptor 2 on the surface of iRBC, but no accumulation of VEGF receptors within the iRBC. Addition of VEGF to parasite cultures had a trophic effect on parasite growth and also partially rescued growth of drug treated parasites. Both these effects were abrogated when parasites were grown in serum-free medium, suggesting a requirement for soluble VEGF receptor. We conclude that P. falciparum iRBC can bind host VEGF-R on the erythrocyte membrane and accumulate host VEGF within the parasitophorous vacuole, which may have a trophic effect on parasite growth.
authors.affiliation: Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Navakanit
authors.initials: N
authors.lastname: Sachanonta
authors.forename: Isabelle M
authors.initials: IM
authors.lastname: Medana
authors.forename: Rachel
authors.initials: R
authors.lastname: Roberts
authors.forename: Margaret
authors.initials: M
authors.lastname: Jones
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: David J P
authors.initials: DJ
authors.lastname: Ferguson
authors.forename: Gareth D H
authors.initials: GD
authors.lastname: Turner
authors.forename: Emsri
authors.initials: E
authors.lastname: Pongponratn
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology; D000077332:Artesunate; D002478:Cells, Cultured; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D016778:Malaria, Falciparum / Q000378:metabolism / Q000469:parasitology*; D018613:Microscopy, Confocal; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D042461:Vascular Endothelial Growth Factor A; D000077332:Artesunate; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2