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Infection and Immunity, June 2004, p. 3344-3349, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3344-3349.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Complement Activation and Complement-Dependent Inflammation by Neisseria meningitidis Are Independent of Lipopolysaccharide

Tom Sprong,1* Anne-Sophie W. Møller,2 Anna Bjerre,3 Elisabeth Wedege,4 Peter Kierulf,2 Jos W. M. van der Meer,1 Petter Brandtzaeg,3 Marcel van Deuren,1 and T. E. Mollnes5

Department of General Internal Medicine, University Medical Centre St. Radboud Nijmegen, Nijmegen, The Netherlands,1 The R & D Group, Department of Clinical Chemistry,2 Department of Paediatrics, Ullevål University Hospital,3 Norwegian Institute of Public Health,4 Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway5

Received 28 November 2003/ Returned for modification 21 January 2004/ Accepted 19 February 2004

Fulminant meningococcal sepsis has been termed the prototypical lipopolysaccharide (LPS)-mediated gram-negative septic shock. Systemic inflammation by activated complement and cytokines is important in the pathogenesis of this disease. We investigated the involvement of meningococcal LPS in complement activation, complement-dependent inflammatory effects, and cytokine or chemokine production. Whole blood anticoagulated with lepirudin was stimulated with wild-type Neisseria meningitidis H44/76 (LPS+), LPS-deficient N. meningitidis H44/76lpxA (LPS–), or purified meningococcal LPS (NmLPS) at concentrations that were relevant to meningococcal sepsis. Complement activation products, chemokines, and cytokines were measured by enzyme-linked immunosorbent assays, and granulocyte CR3 (CD11b/CD18) upregulation and oxidative burst were measured by flow cytometry. The LPS+ and LPS– N. meningitidis strains both activated complement effectively and to comparable extents. Purified NmLPS, used at a concentration matched to the amount present in whole bacteria, did not induce any complement activation. Both CR3 upregulation and oxidative burst were also induced, independent of LPS. Interleukin-1ß (IL-1ß), tumor necrosis factor alpha, and macrophage inflammatory protein 1{alpha} production was predominantly dependent on LPS, in contrast to IL-8 production, which was also markedly induced by the LPS– meningococci. In this whole blood model of meningococcal sepsis, complement activation and the immediate complement-dependent inflammatory effects of CR3 upregulation and oxidative burst occurred independent of LPS.

* Corresponding author. Mailing address: Department of General Internal Medicine, University Medical Centre St. Radboud Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Phone: 31-243618819. Fax: 31-243541734. E-mail: t.sprong{at}aig.umcn.nl.

Editor: J. N. Weiser

Infection and Immunity, June 2004, p. 3344-3349, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3344-3349.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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