title: Influence of acyl chain fluidity on the lipopolysaccharide-induced activation of complement.
abstract: Lipopolysaccharides (LPSs, endotoxins) are the major amphiphilic constituents of the outer leaflet of the outer membrane of Gram-negative bacteria. They are known to activate the complement cascade to form lytic membrane pores. Here, we study the influence of the fluidity of the acyl chains of LPSs and lipid As on the formation of lytic pores. To this end, we have performed electrical measurements on asymmetric planar endotoxin/phospholipid bilayers as a reconstitution model of the outer membrane using two deep rough mutant LPSs (from Escherichia coli strains WBB01 and WBB25) and two lipid As (from E. coli WBB25 and Rhodobacter sphaeroides). The two LPSs and the two lipid As each differ in their acylation pattern which is correlated with the fluidity. The addition of human serum to the endotoxin side of the bilayers led to the formation of membrane pores, and pore formation correlated in each case with acyl chain fluidity, i.e. time required for the first lytic pore to be formed was shorter for the more fluid endotoxin. Furthermore, in the case of LPSs, the activation rate was higher for the more fluid membrane and the respective bacteria had a higher susceptibility to the growth inhibitory action of serum.
authors.affiliation: Research Center Borstel, Center for Medicine and Biosciences, Division of Biophysics, Borstel, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Wiese
authors.forename: P
authors.initials: P
authors.lastname: Grünewald
authors.forename: K J
authors.initials: KJ
authors.lastname: Schaper
authors.forename: U
authors.initials: U
authors.lastname: Seydel
mesh_terms: D000215:Acylation; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology; D003167:Complement Activation / Q000187:drug effects*; D003165:Complement System Proteins / Q000276:immunology*; D004553:Electric Conductivity; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli / Q000254:growth & development / Q000276:immunology; D006090:Gram-Negative Bacteria / Q000254:growth & development / Q000276:immunology; D006801:Humans; D008050:Lipid A / Q000494:pharmacology*; D008051:Lipid Bilayers / Q000276:immunology; D008560:Membrane Fluidity; D012242:Rhodobacter sphaeroides / Q000254:growth & development / Q000276:immunology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D004731:Endotoxins; D008050:Lipid A; D008051:Lipid Bilayers; C044101:endotoxin, Escherichia coli; D003165:Complement System Proteins