J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M300453-JLR200 on February 1, 2004

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Journal of Lipid Research, Vol. 45, 742-749, April 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Human lipoproteins have divergent neutralizing effects on E. coli LPS, N. meningitidis LPS, and complete Gram-negative bacteria

Tom Sprong*,{dagger}, Mihai G. Netea*,{dagger}, Peter van der Ley§, Trees J. G. Verver-Jansen*,{dagger}, Liesbeth E. H. Jacobs*,{dagger}, Anton Stalenhoef*, Jos W. M. van der Meer*,{dagger} and Marcel van Deuren1,*,{dagger}

* Department of General Internal Medicine, University Medical Centre St. Radboud, Nijmegen, The Netherlands
{dagger} Nijmegen University Centre for Infectious Diseases, University Medical Centre St. Radboud, Nijmegen, The Netherlands
§ National Institute of Public Health and the Environment, Bilthoven, The Netherlands

1 To whom correspondence should be addressed. e-mail: m.vandeuren{at}aig.umcn.nl

The use of lipoproteins has been suggested as a treatment for Gram-negative sepsis because they inhibit lipopolysaccharide (LPS)-mediated cytokine production. However, little is known about the neutralizing effects of lipoproteins on cytokine production by meningococcal LPS or whole Gram-negative bacteria. We assessed the neutralizing effect of LDLs, HDLs, and VLDLs on LPS- or whole bacteria-induced cytokines in human mononuclear cells. A strong inhibition of Escherichia coli LPS-induced interleukin-1ß (IL-1ß), tumor necrosis factor-{alpha}, and IL-10 by LDL and HDL was seen, whereas VLDL had a less pronounced effect. In contrast, Neisseria meningitidis LPS, in similar concentrations, was neutralized much less effectively than E. coli LPS. Effective neutralization of meningococcal LPS required a longer interaction time, a lower concentration of LPS, or higher concentrations of lipoproteins. The difference in neutralization was independent of the saccharide tail, suggesting that the lipid A moiety accounted for the difference. Minimal neutralizing effects of the lipoproteins were observed on whole E. coli or N. meningitidis bacteria under all conditions tested.

These results indicate that efficient neutralization of LPS depends on the type of LPS, but a sufficiently long interaction time, a low LPS concentration, or high lipoprotein concentration also inhibited cytokines by the less efficiently neutralized N. meningitidis LPS. Irrespective of these differences, whole bacteria showed no neutralization by lipoproteins.

Supplementary key words Gram-negative sepsis • lipopolysaccharide • low density lipoprotein • high density lipoprotein • very low density lipoprotein • cytokines • mononuclear cells • Escherichia coli • Neisseria meningitidis


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