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dc.contributor.authorSchromm, Andra B.
dc.contributor.authorBrandenburg, Klaus
dc.contributor.authorLoppnow, Harald
dc.contributor.authorMoran, Anthony P.
dc.contributor.authorKoch, Michel H. J.
dc.contributor.authorRietschel, Ernst TH.
dc.contributor.authorSeydel, Ulrich
dc.date.accessioned2018-08-24T08:26:21Z
dc.date.available2018-08-24T08:26:21Z
dc.date.issued2000-04-01
dc.identifier.citationSchromm, Andra B. Brandenburg, Klaus; Loppnow, Harald; Moran, Anthony P.; Koch, Michel H. J.; Rietschel, Ernst TH.; Seydel, Ulrich (2000). Biological activities of lipopolysaccharides are determined by the shape of their lipid a portion. European Journal of Biochemistry 267 (7), 2008-2013
dc.identifier.issn0014-2956
dc.identifier.urihttp://hdl.handle.net/10379/9850
dc.description.abstractLipopolysaccharide (LPS) represents a major virulence factor of Gram-negative bacteria ('endotoxin') that can cause septic shock in mammals including man. The lipid anchor of LPS to the outer membrane, lipid A, has a peculiar chemical structure, harbours the 'endotoxic principle' of LPS and is responsible for the expression of pathophysiological effects. Chemically modified lipid A can be endotoxically inactive, but may express strong antagonistic activity against LPS, a property that can be utilized in antisepsis treatment. We show here that these different biological activities are directly correlated with the molecular shape of lipid A. Only (hexaacyl) lipid A with a conical/concave shape, the cross-section of the hydrophobic region being larger than that of the hydrophilic region, exhibited strong interleukin-6 (IL-6)-inducing capacity. Most strikingly, a correlation between a cylindrical molecular shape of lipid A and antagonistic activity was established: IL-6 induction by enterobacterial LPS was inhibited by cylindrically shaped lipid A except for compounds with reduced headgroup charge. The antagonistic action is interpreted by assuming that lipid A molecules intercalate into the cytoplasmic membrane of mononuclear cells, and subsequently blocking of the putative signaling protein by the lipid A with cylindrical shape.
dc.publisherWiley-Blackwell
dc.relation.ispartofEuropean Journal of Biochemistry
dc.subjectlipid a
dc.subjectmolecular shape
dc.subjectagonism
dc.subjectantagonism
dc.subjectx-ray diffraction
dc.subjectphospholipid-membranes
dc.subjectbacterial-endotoxin
dc.subjectbinding-protein
dc.subjecthuman monocytes
dc.subjectreceptor
dc.subjectlps
dc.subjectmacrophages
dc.subjectrecognition
dc.subjectmolecules
dc.subjectinduction
dc.titleBiological activities of lipopolysaccharides are determined by the shape of their lipid a portion
dc.typeArticle
dc.identifier.doi10.1046/j.1432-1327.2000.01204.x
dc.local.publishedsourcehttp://onlinelibrary.wiley.com/doi/10.1046/j.1432-1327.2000.01204.x/pdf
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