title: Porphyromonas gingivalis lipopolysaccharide lipid A heterogeneity: differential activities of tetra- and penta-acylated lipid A structures on E-selectin expression and TLR4 recognition.
abstract: Porphyromonas gingivalis is a gram-negative bacterium strongly associated with periodontitis, a chronic inflammatory disease of the tissue surrounding the tooth root surface. Lipopolysaccharide (LPS) obtained from P. gingivalis is unusual in that it has been shown to display an unusual amount of lipid A heterogeneity containing both tetra- and penta-acylated lipid A structures. In this report, it is shown that penta-acylated lipid A structures facilitate E-selectin expression whereas tetra-acylated lipid A structures do not. Furthermore, it is shown that tetra-acylated lipid A structures are potent antagonists for E-selectin expression. Both tetra- and penta-acylated lipid A structures interact with TLR4 although experiments utilizing human, mouse and human/mouse chimeric TLR4 proteins demonstrated that they interact differentially with the TLR4 signalling complexes. The presence of two different structural types of lipid A in P. gingivalis LPS, with opposing effects on the E-selectin response suggests that this organism is able to modulate innate host responses by alterations in the relative amount of these lipid A structures.
authors.affiliation: Department of Periodontics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Reife
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Coats
authors.forename: Montaser
authors.initials: M
authors.lastname: Al-Qutub
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Dixon
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Braham
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Billharz
authors.forename: William N
authors.initials: WN
authors.lastname: Howald
authors.forename: Richard P
authors.initials: RP
authors.lastname: Darveau
mesh_terms: D000818:Animals; D002460:Cell Line; D019040:E-Selectin / Q000096:biosynthesis*; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D008050:Lipid A / Q000737:chemistry / Q000502:physiology*; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D051379:Mice; D008833:Microcirculation / Q000166:cytology; D016966:Porphyromonas gingivalis / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D019040:E-Selectin; D008050:Lipid A; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4