title: An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration.
abstract: The sequestration of parasitized erythrocytes in the microvasculature of vital organs is central to the pathogenesis of severe Plasmodium falciparum malaria. This process is mediated by specific interactions between parasite adherence ligands and host receptors on vascular endothelium such as intercellular adhesion molecule-1 (ICAM-1) and CD36. Using immunohistochemistry we have examined the distribution of putative sequestration receptors in different organs from fatal cases of P. falciparum malaria and noninfected controls. Receptor expression and parasite sequestration in the brain were quantified and correlated. Fatal malaria was associated with widespread induction of endothelial activation markers, with significantly higher levels of ICAM-1 and E-selectin expression on vessels in the brain. In contrast, cerebral endothelial CD36 and thrombospondin staining were sparse, with no evidence for increased expression in malaria. There was highly significant co-localization of sequestration with the expression of ICAM-1, CD36, and E-selectin in cerebral vessels but no cellular inflammatory response. These results suggest that these receptors have a role in sequestration in vivo and indicate that systemic endothelial activation is a feature of fatal malaria.
authors.affiliation: Molecular Parasitology Group, John Radcliffe Hospital, Oxford, UK.
authors.forename: G D
authors.initials: GD
authors.lastname: Turner
authors.forename: H
authors.initials: H
authors.lastname: Morrison
authors.forename: M
authors.initials: M
authors.lastname: Jones
authors.forename: T M
authors.initials: TM
authors.lastname: Davis
authors.forename: S
authors.initials: S
authors.lastname: Looareesuwan
authors.forename: I D
authors.initials: ID
authors.lastname: Buley
authors.forename: K C
authors.initials: KC
authors.lastname: Gatter
authors.forename: C I
authors.initials: CI
authors.lastname: Newbold
authors.forename: S
authors.initials: S
authors.lastname: Pukritayakamee
authors.forename: B
authors.initials: B
authors.lastname: Nagachinta
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001921:Brain / Q000276:immunology / Q000469:parasitology; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules / Q000032:analysis; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000276:immunology*; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology*; D016779:Malaria, Cerebral / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum
chemical_list: D015703:Antigens, CD; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D018799:Intercellular Adhesion Molecule-1