title: Systemic endothelial activation occurs in both mild and severe malaria. Correlating dermal microvascular endothelial cell phenotype and soluble cell adhesion molecules with disease severity.
abstract: Fatal Plasmodium falciparum malaria is accompanied by systemic endothelial activation. To study endothelial activation directly during malaria and sepsis in vivo, the expression of cell adhesion molecules on dermal microvascular endothelium was examined in skin biopsies and correlated with plasma levels of soluble (circulating) ICAM-1, E-selectin, and VCAM-1 and the cytokine tumor necrosis factor (TNF)-alpha. Skin biopsies were obtained from 61 cases of severe malaria, 42 cases of uncomplicated malaria, 10 cases of severe systemic sepsis, and 17 uninfected controls. Systemic endothelial activation, represented by the up-regulation of inducible cell adhesion molecules (CAMs) on endothelium and increased levels of soluble CAMs (sCAMs), were seen in both severe and uncomplicated malaria and sepsis when compared with uninfected controls. Plasma levels of sICAM-1, sVCAM-1, and sE-selectin correlated positively with the severity of malaria whereas TNF-alpha was raised nonspecifically in malaria and sepsis. Immunohistochemical evidence of endothelial activation in skin biopsies did not correlate with sCAM levels or disease severity. This indicates a background of systemic endothelial activation, which occurs in both mild and severe malaria and sepsis. The levels of sCAMs in malaria are thus not an accurate reflection of endothelial cell expression of CAMs in a particular vascular bed, and other factors must influence their levels during disease.
authors.affiliation: University Department of Cellular Science, John Radcliffe Hospital, Oxford, United Kingdom. gareth.turner@cellsci.ox.ac.uk
authors.forename: G D
authors.initials: GD
authors.lastname: Turner
authors.forename: V C
authors.initials: VC
authors.lastname: Ly
authors.forename: T H
authors.initials: TH
authors.lastname: Nguyen
authors.forename: T H
authors.initials: TH
authors.lastname: Tran
authors.forename: H P
authors.initials: HP
authors.lastname: Nguyen
authors.forename: D
authors.initials: D
authors.lastname: Bethell
authors.forename: S
authors.initials: S
authors.lastname: Wyllie
authors.forename: K
authors.initials: K
authors.lastname: Louwrier
authors.forename: S B
authors.initials: SB
authors.lastname: Fox
authors.forename: K C
authors.initials: KC
authors.lastname: Gatter
authors.forename: N P
authors.initials: NP
authors.lastname: Day
authors.forename: T H
authors.initials: TH
authors.lastname: Tran
authors.forename: N J
authors.initials: NJ
authors.lastname: White
authors.forename: A R
authors.initials: AR
authors.lastname: Berendt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000097:blood / Q000378:metabolism*; D002648:Child; D019040:E-Selectin / Q000097:blood / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000378:metabolism; D008288:Malaria / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood / Q000378:metabolism; D012867:Skin / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1