title: Endothelial adhesion molecule expression and its inhibition by recombinant bactericidal/permeability-increasing protein are influenced by the capsulation and lipooligosaccharide structure of Neisseria meningitidis.
abstract: Vascular endothelial injury is responsible for many of the clinical manifestations of severe meningococcal disease. Binding and migration of activated host inflammatory cells is a central process in vascular damage. The expression and function of adhesion molecules regulate interactions between leukocytes and endothelial cells. Little is known about how meningococci directly influence these receptors. In this study we have explored the effect of Neisseria meningitidis on endothelial adhesion molecule expression and found this organism to be a potent inducer of the adhesion molecules CD62E, ICAM-1, and VCAM-1. Exposure of endothelium to a serogroup B strain of Neisseria meningitidis, B1940, and a range of isogenic mutants revealed that lipooligosaccharide (LOS) structure and capsulation influence the expression of adhesion molecules. Following only a brief exposure (15 min) to the bacteria, there were large differences in the capacity of the different mutants to induce vascular cell adhesion molecules, with the unencapsulated and truncated LOS strains being most potent (P < 0.05). Furthermore, the pattern of cell adhesion molecule expression was different with purified endotoxin from that with intact bacteria. Meningococci were more potent stimuli of CD62E expression than was endotoxin, whereas endotoxin was at least as effective as meningococci in inducing ICAM-1 and VCAM-1. The effect of bactericidal/permeability increasing protein (rBPI(21)), an antibacterial molecule with antiendotoxin properties, was also dependent on LOS structure. The strains which possessed a truncated or nonsialylated LOS, whether capsulated or not, were more sensitive to the inhibitory effects of rBPI(21). These findings could have important implications for the use of antiendotoxin therapy in meningococcal disease.
authors.affiliation: Immunobiology Unit, Institute of Child Health, London, United Kingdom. G.dixon@ich.ucl.ac.uk
authors.forename: G L
authors.initials: GL
authors.lastname: Dixon
authors.forename: R S
authors.initials: RS
authors.lastname: Heyderman
authors.forename: K
authors.initials: K
authors.lastname: Kotovicz
authors.forename: D L
authors.initials: DL
authors.lastname: Jack
authors.forename: S R
authors.initials: SR
authors.lastname: Andersen
authors.forename: U
authors.initials: U
authors.lastname: Vogel
authors.forename: M
authors.initials: M
authors.lastname: Frosch
authors.forename: N
authors.initials: N
authors.lastname: Klein
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D016667:Bacterial Capsules / Q000502:physiology*; D001798:Blood Proteins / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000494:pharmacology; D008565:Membrane Proteins; D009345:Neisseria meningitidis / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; C021623:bactericidal permeability increasing protein; C023023:lipid-linked oligosaccharides; D018799:Intercellular Adhesion Molecule-1