The influence of capsulation and lipooligosaccharide structure on neutrophil adhesion molecule expression and endothelial injury by Neisseria meningitidis.
Host inflammatory response to meningococcal infection is believed to be a major determinant of disease severity. Isogenic mutants of Neisseria meningitidis serogroup B1940, which differ in expression of capsular polysaccharide and lipooligosaccharide (LOS), were used to examine host responses in a whole blood model of bacteremia and a model of endothelial injury. The parent organism caused significantly less neutrophil shedding of the adhesion molecule, L-selectin, than the three mutant organisms (P < .01) and was most resistant to the bactericidal activity of whole blood. Despite marked differences in bacterial adhesion to endothelial cells (P < .05), no damage was induced by organisms alone. Endothelial injury was observed when neutrophils were incubated with adherent, capsule-deficient organisms (P < .05). The degree of endothelial damage was related to the number of neutrophils adherent to the endothelium. Thus, bacterial capsulation and LOS structure can influence neutrophil activation and endothelial injury and, as such, may be important in the pathogenesis of meningococcal sepsis.
Immunobiology Unit, Institute of Child Health, London, United Kingdom.
N J
NJ
Klein
C A
CA
Ison
M
M
Peakman
M
M
Levin
S
S
Hammerschmidt
M
M
Frosch
R S
RS
Heyderman
D000942:Antigens, Bacterial / Q000502:physiology; D001422:Bacterial Adhesion / Q000502:physiology; D016667:Bacterial Capsules / Q000502:physiology*; D001798:Blood Proteins / Q000096:biosynthesis; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000382:microbiology / Q000473:pathology* / Q000502:physiology; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D019041:L-Selectin / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry*; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009345:Neisseria meningitidis / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011135:Polysaccharides, Bacterial / Q000502:physiology; D014471:Umbilical Veins
D000942:Antigens, Bacterial; D001798:Blood Proteins; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006497:Heparan Sulfate; D019041:L-Selectin; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011135:Polysaccharides, Bacterial; C030340:elastin microfibril interface located protein; C023023:lipid-linked oligosaccharides