title: Brain endothelial cells increase the proliferation of Plasmodium falciparum through production of soluble factors.
abstract: We here describe the novel finding that brain endothelial cells in vitro can stimulate the growth of Plasmodium falciparum through the production of low molecular weight growth factors. By using a conditioned medium approach, we show that the brain endothelial cells continued to release these factors over time. If this mirrors the in vivo situation, these growth factors potentially would provide an advantage, in terms of enhanced growth, for sequestered parasitised red blood cells in the brain microvasculature. We observed this phenomenon with brain endothelial cells from several sources as well as a second P. falciparum strain. The characteristics of the growth factors included: <3 kDa molecular weight, heat stable, and in part chloroform soluble. Future efforts should be directed at identifying these growth factors, since blocking their production or actions might be of benefit for reducing parasite load and, hence, malaria pathology.
authors.affiliation: Molecular Immunopathology Unit, School of Medical Sciences and Bosch Institute, Sydney Medical School, University of Sydney, NSW 2006, Australia; Department of Parasitology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: L T
authors.initials: LT
authors.lastname: Khaw
authors.affiliation: Molecular Immunopathology Unit, School of Medical Sciences and Bosch Institute, Sydney Medical School, University of Sydney, NSW 2006, Australia.
authors.forename: H J
authors.initials: HJ
authors.lastname: Ball
authors.affiliation: Molecular Immunopathology Unit, School of Medical Sciences and Bosch Institute, Sydney Medical School, University of Sydney, NSW 2006, Australia; Immune Imaging Program, Centenary Institute, Sydney, NSW 2050, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Mitchell
authors.affiliation: Vascular Immunology Unit, School of Medical Sciences and Bosch Institute, Sydney Medical School, University of Sydney, NSW 2006, Australia.
authors.forename: G E
authors.initials: GE
authors.lastname: Grau
authors.affiliation: Vascular Biology Division, Victor Chang Cardiac Research Institute, Lowy Packer Building, 405 Liverpool Street, Darlinghurst, NSW 2010, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Stocker
authors.affiliation: Department of Microbiology and Molecular Genetics, Kuvin Centre for the Study of Tropical and Infectious Diseases, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: J
authors.initials: J
authors.lastname: Golenser
authors.affiliation: Molecular Immunopathology Unit, School of Medical Sciences and Bosch Institute, Sydney Medical School, University of Sydney, NSW 2006, Australia. Electronic address: nicholas.hunt@sydney.edu.au.
authors.forename: N H
authors.initials: NH
authors.lastname: Hunt
mesh_terms: D000953:Antigens, Protozoan / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000469:parasitology*; D002460:Cell Line; D017077:Culture Media, Conditioned; D004727:Endothelium / Q000166:cytology / Q000378:metabolism / Q000469:parasitology; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D019271:Hypoxanthine / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000254:growth & development*; D015800:Protozoan Proteins / Q000032:analysis / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D017077:Culture Media, Conditioned; C514457:HRP-2 antigen, Plasmodium falciparum; D036341:Intercellular Signaling Peptides and Proteins; D015800:Protozoan Proteins; D019271:Hypoxanthine
keywords: Cerebral malaria; Malaria; Plasmodium falciparum