Escherichia coli and Porphyromonas gingivalis lipopolysaccharide interactions with CD14: implications for myeloid and nonmyeloid cell activation.
Porphyromonas gingivalis, a gram-negative bacterium, is an etiologic agent for adult periodontitis. Lipopolysaccharide (LPS) released from this bacterium can react with numerous host cell types. P. gingivalis LPS stimulates tumor necrosis factor alpha and interleukin-1beta secretion from monocytes (myeloid) but does not elicit E-selectin expression from human endothelial cells (nonmyeloid). In contrast, Escherichia coli LPS facilitates expression of these inflammatory mediators through CD14-dependent pathways on both myeloid and nonmyeloid cells. LPS binding studies have revealed that although P. gingivalis and E. coli LPSs bind to CD14 differently, this fact does not adequately explain the lack of endothelial cell activation by P. gingivalis LPS. Rather, LPS binding site and blocking monoclonal antibody epitope mapping studies have suggested that CD14 presents a charged surface that captures different microbial ligands by electrostatic interactions. We propose that human endothelial cells do not respond to P. gingivalis LPS because of their inability to "recognize" CD14-P. gingivalis LPS complexes.
Cunningham
M D
MD
Bristol-Myers Squibb Pharmaceutical Research Institute, and the Department of Periodontics, University of Washington, Seattle 98121, USA.
Bajorath
J
J
Somerville
J E
JE
Darveau
R P
RP
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology*; D017354:Point Mutation; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000378:metabolism; D014471:Umbilical Veins
D019040:E-Selectin; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides