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Clinical and Diagnostic Laboratory Immunology, May 1998, p. 355-361, Vol. 5, No. 3
1071-412X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The Tumor Necrosis Factor-Inducing Potency of Lipopolysaccharide and Uronic Acid Polymers Is Increased when They Are Covalently Linked to Particles

Gøril Berntzen,1 Trude H. Flo,1 Andrei Medvedev,1 Lars Kilaas,2 Gudmund Skjåk-Bræk,3 Anders Sundan,1 and Terje Espevik1,*

Institute of Cancer Research and Molecular Biology,1 SINTEF, Division of Applied Chemistry,2 and Institute of Biotechnology,3 The Norwegian University of Science and Technology, N-7005 Trondheim, Norway

Received 25 September 1997/Returned for modification 15 December 1997/Accepted 3 March 1998

Lipopolysaccharide (LPS) and polymers of the uronic acid family stimulate monocytes to produce tumor necrosis factor (TNF). The TNF-inducing potency of these polysaccharides may depend on their supramolecular configuration. In this study detoxified LPS and uronic acid polymers have been covalently linked to particles which have been added to monocytes under serum-free conditions. Reducing the size of mannuronan from 350,000 to 5,500 Da (M-blocks) led to a 10- to 100-fold reduction in TNF-inducing potency. However, covalently linking the M-blocks to monodisperse suspensions of magnetic particles increased the TNF-inducing potency by up to 60,000-fold. Also, the TNF-inducing potency of glucuronic acid polymers was increased when they were linked to particles, but no potentiation was observed with guluronic acid blocks covalently attached to particles. Furthermore, O chains of LPS (detoxified LPS) became potent TNF inducers when they were presented to monocytes on a particle surface. No activation of the LPS-responsive SW480 adenocarcinoma cells was found with detoxified LPS or M-block particles, suggesting a preference for cells expressing CD14 and/or other membrane molecules. The potentiating effects were not restricted to polymers attached to aminated magnetic particles. Of particular interest, we found that short blocks of mannuronan induced TNF production also when covalently linked to biodegradable, bovine serum albumin particles.

* Corresponding author. Mailing address: Institute of Cancer Research and Molecular Biology, University Medical Center, NTNU, N-7005 Trondheim, Norway. Phone: 47-73-59-86-68. Fax: 47-73-59-88-01. E-mail: terje.espevik{at}medisin.ntnu.no.

Clinical and Diagnostic Laboratory Immunology, May 1998, p. 355-361, Vol. 5, No. 3
1071-412X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Lagoumintzis, G., Christofidou, M., Dimitracopoulos, G., Paliogianni, F. (2003). Pseudomonas aeruginosa Slime Glycolipoprotein Is a Potent Stimulant of Tumor Necrosis Factor Alpha Gene Expression and Activation of Transcription Activators Nuclear Factor {kappa}B and Activator Protein 1 in Human Monocytes. Infect. Immun. 71: 4614-4622 [Abstract] [Full Text]  
  • Flo, T. H., Ryan, L., Latz, E., Takeuchi, O., Monks, B. G., Lien, E., Halaas, O., Akira, S., Skjak-Brak, G., Golenbock, D. T., Espevik, T. (2002). Involvement of Toll-like Receptor (TLR) 2 and TLR4 in Cell Activation by Mannuronic Acid Polymers. J. Biol. Chem. 277: 35489-35495 [Abstract] [Full Text]  
  • Flo, T. H., Ryan, L., Kilaas, L., Skjak-Brak, G., Ingalls, R. R., Sundan, A., Golenbock, D. T., Espevik, T. (2000). Involvement of CD14 and beta 2-Integrins in Activating Cells with Soluble and Particulate Lipopolysaccharides and Mannuronic Acid Polymers. Infect. Immun. 68: 6770-6776 [Abstract] [Full Text]  


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