title: Endothelial glycocalyx on brain endothelial cells is lost in experimental cerebral malaria.
abstract: We hypothesized that the glycocalyx, which is important for endothelial integrity, is lost in severe malaria. C57BL/6 mice were infected with Plasmodium berghei ANKA, resulting in cerebral malaria, or P. chabaudi AS, resulting in uncomplicated malaria. We visualized the glycocalyx with transmission electron microscopy and measured circulating glycosaminoglycans by dot blot and ELISA. The glycocalyx was degraded in brain vasculature in cerebral and to a lesser degree uncomplicated malaria. It was affected on both intact and apoptotic endothelial cells. Circulating glycosaminoglycan levels suggested that glycocalyx disruption preceded cerebral manifestations. The contribution of this loss to pathogenesis should be studied further.
authors.affiliation: Centre for Medical Parasitology, Department of Clinical Microbiology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Casper
authors.initials: C
authors.lastname: Hempel
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Poul
authors.initials: P
authors.lastname: Hyttel
authors.affiliation: Centre for Medical Parasitology, Department of Clinical Microbiology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Jørgen A L
authors.initials: JA
authors.lastname: Kurtzhals
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019276:Glycocalyx / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000097:blood; D015151:Immunoblotting; D016779:Malaria, Cerebral / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission
chemical_list: D006025:Glycosaminoglycans
references.citation: Infect Immun. 2000 Jul;68(7):4135-44
references.pmid: 10858230
references.citation: Pflugers Arch. 2007 Jun;454(3):345-59
references.pmid: 17256154
references.citation: J Biol Chem. 1998 Sep 18;273(38):24470-8
references.pmid: 9733739
references.citation: Electrophoresis. 2002 Sep;23(19):3270-7
references.pmid: 12373753
references.citation: Nat Methods. 2012 Jun 28;9(7):676-82
references.pmid: 22743772
references.citation: Cell Microbiol. 2011 Feb;13(2):198-209
references.pmid: 21029292
references.citation: Shock. 2010 Aug;34(2):133-9
references.pmid: 20634656
references.citation: Basic Res Cardiol. 2009 Jan;104(1):78-89
references.pmid: 18836678
references.citation: PLoS One. 2012;7(4):e34509
references.pmid: 22529919
references.citation: Blood. 2013 Aug 1;122(5):842-51
references.pmid: 23741007
references.citation: Am J Pathol. 2011 Oct;179(4):1939-50
references.pmid: 21854739
references.citation: Malar J. 2012 Jun 28;11:216
references.pmid: 22741599
references.citation: Nature. 2013 Jun 27;498(7455):502-5
references.pmid: 23739325
references.citation: Blood. 2003 Mar 15;101(6):2405-11
references.pmid: 12433689