dc.contributor.author | Schromm, Andra B. | |
dc.contributor.author | Brandenburg, Klaus | |
dc.contributor.author | Loppnow, Harald | |
dc.contributor.author | Moran, Anthony P. | |
dc.contributor.author | Koch, Michel H. J. | |
dc.contributor.author | Rietschel, Ernst TH. | |
dc.contributor.author | Seydel, Ulrich | |
dc.date.accessioned | 2018-08-24T08:26:21Z | |
dc.date.available | 2018-08-24T08:26:21Z | |
dc.date.issued | 2000-04-01 | |
dc.identifier.citation | Schromm, 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.issn | 0014-2956 | |
dc.identifier.uri | http://hdl.handle.net/10379/9850 | |
dc.description.abstract | Lipopolysaccharide (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.publisher | Wiley-Blackwell | |
dc.relation.ispartof | European Journal of Biochemistry | |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.subject | lipid a | |
dc.subject | molecular shape | |
dc.subject | agonism | |
dc.subject | antagonism | |
dc.subject | x-ray diffraction | |
dc.subject | phospholipid-membranes | |
dc.subject | bacterial-endotoxin | |
dc.subject | binding-protein | |
dc.subject | human monocytes | |
dc.subject | receptor | |
dc.subject | lps | |
dc.subject | macrophages | |
dc.subject | recognition | |
dc.subject | molecules | |
dc.subject | induction | |
dc.title | Biological activities of lipopolysaccharides are determined by the shape of their lipid a portion | |
dc.type | Article | |
dc.identifier.doi | 10.1046/j.1432-1327.2000.01204.x | |
dc.local.publishedsource | http://onlinelibrary.wiley.com/doi/10.1046/j.1432-1327.2000.01204.x/pdf | |
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