Endotoxic activity and chemical structure of lipopolysaccharides from Chlamydia trachomatis serotypes E and L2 and Chlamydophila psittaci 6BC.
The lipopolysaccharide (LPS) of Chlamydia trachomatis serotype E was isolated from tissue culture-grown elementary bodies and analyzed structurally by mass spectrometry and 1H, 13C and 31P nuclear magnetic resonance. The LPS is composed of the same pentasaccharide bisphosphate alphaKdo-(2-8)-alphaKdo-(2-4)-alphaKdo-(2-6)-betaGlcN-4P-(1-6)-alphaGlcN-1P (Kdo is 3-deoxy-alpha-d-manno-oct-2-ulosonic acid) as reported for C. trachomatis serotype L2[Rund, S., Lindner, B., Brade, H. and Holst, O. (1999) J. Biol. Chem. 274, 16819-16824]. The glucosamine disaccharide backbone is substituted with a complex mixture of fatty acids with ester or amide linkage whereby no ester-linked hydroxy fatty acids were found. The LPS was purified carefully (with contaminations by protein or nucleic acids below 0.3%) and tested for its ability to induce proinflammatory cytokines in several readout systems in comparison to LPS from C. trachomatis serotype L2 and Chlamydophila psittaci strain 6BC as well as enterobacterial smooth and rough LPS and synthetic hexaacyl lipid A. The chlamydial LPS were at least 10 times less active than typical endotoxins; specificity of the activities was confirmed by inhibition with the LPS antagonist, B1233, or with monoclonal antibodies against chlamydial LPS. Like other LPS, the chlamydial LPS used toll-like receptor TLR4 for signalling, but unlike other LPS activation was strictly CD14-dependent.
Heine
Holger
H
Research Center Borstel, Center for Medicine and Biosciences, Borstel, Germany.
Müller-Loennies
Sven
S
Brade
Lore
L
Lindner
Buko
B
Brade
Helmut
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016466:CHO Cells / Q000378:metabolism; D002690:Chlamydia Infections; D002692:Chlamydia trachomatis / Q000737:chemistry* / Q000145:classification; D002691:Chlamydophila psittaci / Q000737:chemistry* / Q000145:classification; D006224:Cricetinae; D029721:Drosophila Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D005227:Fatty Acids / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D011956:Receptors, Cell Surface / Q000378:metabolism; D012703:Serotyping; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014162:Transfection
D000911:Antibodies, Monoclonal; D029721:Drosophila Proteins; D005227:Fatty Acids; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors