%0 Journal Article %1 dixon_endothelial_1999 %A Dixon, G L %A Heyderman, R S %A Kotovicz, K %A Jack, D L %A Andersen, S R %A Vogel, U %A Frosch, M %A Klein, N %D 1999 %J Infection and Immunity %K Adhesion Agents, Antimicrobial Bacterial Blood Capsules, Cationic Cell Cells, Cultured, Endothelium, Humans, Intercellular Lipopolysaccharides, Membrane Molecule-1 Molecule-1, Molecules, Neisseria Peptides, Proteins, Recombinant Vascular Vascular, meningitidis, {Anti-Bacterial} {E-Selectin}, %N 11 %P 5626--5633 %T Endothelial adhesion molecule expression and its inhibition by recombinant bactericidal/permeability-increasing protein are influenced by the capsulation and lipooligosaccharide structure of Neisseria meningitidis %U http://www.ncbi.nlm.nih.gov/pubmed/10531209 %V 67 %X 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 \textless 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.

@article{dixon_endothelial_1999, 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} {\textless} 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.}, added-at = {2011-06-24T11:21:47.000+0200}, author = {Dixon, G L and Heyderman, R S and Kotovicz, K and Jack, D L and Andersen, S R and Vogel, U and Frosch, M and Klein, N}, biburl = {https://www.bibsonomy.org/bibtex/2c2b4ff67e60828a905ec4eab55142be1/ag_vogel}, interhash = {d16b4ed627a4a78bd1ed47e790f00015}, intrahash = {c2b4ff67e60828a905ec4eab55142be1}, issn = {0019-9567}, journal = {Infection and Immunity}, keywords = {Adhesion Agents, Antimicrobial Bacterial Blood Capsules, Cationic Cell Cells, Cultured, Endothelium, Humans, Intercellular Lipopolysaccharides, Membrane Molecule-1 Molecule-1, Molecules, Neisseria Peptides, Proteins, Recombinant Vascular Vascular, meningitidis, {Anti-Bacterial} {E-Selectin},}, month = nov, note = {{PMID:} 10531209}, number = 11, pages = {5626--5633}, timestamp = {2011-06-24T11:21:51.000+0200}, 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}, url = {http://www.ncbi.nlm.nih.gov/pubmed/10531209}, volume = 67, year = 1999 }