title: In vitro study of malaria parasite induced disruption of blood-brain barrier.
abstract: The mechanism of blood-brain barrier breakdown in the complex pathogenesis of cerebral malaria is not well understood. In this study, primary cultures of porcine brain capillary endothelial cells (PBCEC) were used as in vitro model. Membrane-associated malaria antigens obtained from lysed Plasmodium falciparum schizont-infected erythrocytes stimulated human peripheral blood mononuclear cells (PBMC) to secrete tumor necrosis factor alpha. In co-cultivation with the brain endothelial cell model, the malaria-activated PBMC stimulated the expression of E-selectin and ICAM-1 on the PBCEC. Using electric cell-substrate impedance sensing, we detected a significant decrease of endothelial barrier function within 4h of incubation with the malaria-activated PBMC. Correspondingly, immunocytochemical studies showed the disruption of tight junctional complexes. Combination of biochemical and biophysical techniques provides a promising tool to study changes in the blood-brain barrier function associated with cerebral malaria. Moreover, it is shown that the porcine endothelial model is able to respond to human inflammatory cells.
authors.affiliation: Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Lertyot
authors.initials: L
authors.lastname: Treeratanapiboon
authors.forename: Katherina
authors.initials: K
authors.lastname: Psathaki
authors.forename: Joachim
authors.initials: J
authors.lastname: Wegener
authors.forename: Sornchai
authors.initials: S
authors.lastname: Looareesuwan
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Galla
authors.forename: Rachanee
authors.initials: R
authors.lastname: Udomsangpetch
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D001812:Blood-Brain Barrier; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D010963:Plasmodium falciparum / Q000276:immunology / Q000502:physiology*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000953:Antigens, Protozoan; D014409:Tumor Necrosis Factor-alpha