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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
Authors: Gareth D.H. Turner
Heather Morrison
Margaret Jones
Timothy M.E. Davis
Sornchai Looareesuwan
Ian D. Buley
Kevin C. Gatter
Christopher I. Newbold
Sasithon Pukritayakamee
Bussarin Nagachinta
Nicholas J. White
Anthony R. Berendt
John Radcliffe Hospital
Mahidol University
Polpaholpayuhasena Hospital
University of Western Australia
Keywords: Medicine
Issue Date: 1-Nov-1994
Citation: American Journal of Pathology. Vol.145, No.5 (1994), 1057-1069
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.
ISSN: 00029440
Appears in Collections:Scopus 1991-2000

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