* Department of Internal Medicine, University Medical Center Nijmegen, Nijmegen, and
National Institute of Public Health and the Environment, Bilthoven, The Netherlands; and
Institute of Child Health, University College London Medical School, London, United Kingdom
Correspondence: Marcel van Deuren, Department of Internal Medicine, University Medical Centre Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: m.vandeuren{at}AIG.AZN.NL
To determine the relative contribution of lipopolysaccharide (LPS) and
non-LPS components of Neisseria meningitidis to the
pathogenesis of meningococcal sepsis, this study quantitatively
compared cytokine induction by isolated LPS, wild-type serogroup
B meningococci (strain H44/76), and LPS-deficient mutant
meningococci (strain H44/76[pLAK33]). Stimulation of human
peripheral-blood mononuclear cells with wild-type and LPS-deficient
meningococci showed that non-LPS components of meningococci are
responsible for a substantial part of tumor necrosis factor (TNF)-
and interleukin (IL)-1ß production and virtually all interferon
(IFN)-
production. Based on tricine sodium dodecyl
sulfate-polyacrylamide gel electrophoresis analysis of LPS in
proteinase K-treated lysates of N. meningitidis H44/76, a
quantitative comparison was made between the cytokine-inducing capacity
of isolated and purified LPS and LPS-containing meningococci. At
concentrations of >107 bacteria/mL, intact bacteria were
more potent cytokine inductors than equivalent amounts of isolated LPS,
and cytokine induction by non-LPS components was additive to that by
LPS. Experiments with mice showed that non-LPS components of
meningococci were able to induce cytokine production and mortality. The
principal conclusion is that non-LPS parts of N.
meningitidis may play a role in the pathogenesis of meningococcal
sepsis by inducing substantial TNF-, IL-1ß, and IFN-
production.
Key Words: LPS-deficient meningococci • meningococcal sepsis • outer membrane • 2-keto-3-deoxyoctanate • TSDS-PAGE
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