title: Experimental cerebral malaria develops independently of endothelial expression of intercellular adhesion molecule-1 (icam-1).
abstract: Cerebral malaria (CM) is a severe clinical complication of Plasmodium falciparum malaria infection and is characterized by a high fatality rate and neurological damage. Sequestration of parasite-infected red blood cells in brain microvasculature utilizes host- and parasite-derived adhesion molecules and is an important factor in the development of CM. ICAM-1, an alternatively spliced adhesion molecule, is believed to be critical on endothelial cells for infected red blood cell sequestration in CM. Using ICAM-1 mutant mice, we found that the full-length ICAM-1 isoform is not required for development of murine experimental CM (ECM) and that ECM phenotype varies with the combination of ICAM-1 isoforms expressed. Furthermore, we observed development of ECM in transgenic mice expressing ICAM-1 only on leukocytes, indicating that endothelial cell expression of this adhesion molecule is not required for disease pathogenesis. We propose that ICAM-1-dependent cellular aggregation, independent of ICAM-1 expression on the cerebral microvasculature, contributes to ECM.
authors.affiliation: Department of Microbiology and Neurology, University of Alabama, Birmingham, Alabama 35294, USA.
authors.forename: Theresa N
authors.initials: TN
authors.lastname: Ramos
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bullard
authors.forename: Meghan M
authors.initials: MM
authors.lastname: Darley
authors.forename: Kristin
authors.initials: K
authors.lastname: McDonald
authors.forename: David F
authors.initials: DF
authors.lastname: Crawford
authors.forename: Scott R
authors.initials: SR
authors.lastname: Barnum
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000469:parasitology / Q000473:pathology; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D016779:Malaria, Cerebral / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D008833:Microcirculation; D010963:Plasmodium falciparum / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics
chemical_list: D020033:Protein Isoforms; D018799:Intercellular Adhesion Molecule-1