High-level endothelial E-selectin (CD62E) cell adhesion molecule expression by a lipopolysaccharide-deficient strain of Neisseria meningitidis despite poor activation of NF-kappaB transcription factor.
Binding of host inflammatory cells to the endothelium is a critical contributor to the vascular damage characteristic of severe meningococcal disease and is regulated by endothelial cell adhesion molecules such as ICAM-1, VCAM-1 and CD62E. Intact meningococci induce far higher levels of CD62E than lipopolysaccharide (LPS) alone, whereas LPS is at least as potent as meningococci at inducing both VCAM-1 and ICAM-1 expression. This suggests that meningococci possess additional factors other than LPS present in whole bacteria that result in differential adhesion molecule expression. To investigate this possibility, we studied the capacity of an LPS-deficient isogenic strain of serogroup B Neisseria meningitidis H44/76 (lpxA-) to induce endothelial cell adhesion molecule expression and translocation of the transcription factor NF-kappaB, and compared it to both parent and unencapsulated strains of both B1940 and H44/76 and purified LPS. Although the LPS-deficient isogenic mutant of strain H44/76 was found to be a poor inducer of NF-kappaB, it induced higher levels of CD62E expression than LPS alone. These data provide evidence that intact meningococci induce a range of signals in the endothelium that are distinct from those seen with purified LPS alone and that they occur in a LPS-dependent and LPS-independent manner. These signals may explain the potent effects of N. meningitidis on CD62E expression on vascular endothelium and provide a basis for the complex endothelial dysregulation seen in meningococcal sepsis.
Dixon
G L J
GL
Immunobiology Unit, Institute of Child Health, London, UK. G.Dixon@ich.ucl.ac.uk
Heyderman
R S
RS
van der Ley
P
P
Klein
N J
NJ
D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D009345:Neisseria meningitidis / Q000235:genetics / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D019040:E-Selectin; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1