Abstract |
Glucans are fungal cell wall polysaccharides which stimulate innate immune responses. We determined the minimum unit ligand that would bind to glucan receptors on human U937 cells using laminarin-derived pentaose, hexaose, and heptaose glucan polymers. When U937 membranes were pretreated with the oligosaccharides and passed over a glucan surface, only the heptasaccharide inhibited the interaction of glucan with membrane receptors at a K(d) of 31 microM (95% CI 20-48 microM) and 100% inhibition. However, the glucan heptasaccharide did not stimulate U937 monocyte NFkappaB signaling, nor did it increase survival in a murine model of polymicrobial sepsis. Laminarin, a larger and more complex glucan polymer (M(w) = 7700 g/mol), only partially inhibited binding (61 +/- 4%) at a K(d) of 2.6 microM (99% CI 1.7-4.2 microM) with characteristics of a single binding site. These results indicate that a heptasaccharide is the smallest unit ligand recognized by macrophage glucan receptors. The data also indicate the presence of at least two glucan-binding sites on U937 cells and that the binding sites on human monocyte/macrophages can discriminate between glucan polymers. The heptasaccharide and laminarin were receptor antagonists, but they were not receptor agonists with respect to activation of NFkappaB-dependent signaling pathways or protection against experimental sepsis.
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Authors | E Lowe, P Rice, T Ha, C Li, J Kelley, H Ensley, J Lopez-Perez, J Kalbfleisch, D Lowman, P Margl, W Browder, D Williams |
Journal | Microbes and infection
(Microbes Infect)
Vol. 3
Issue 10
Pg. 789-97
(Aug 2001)
ISSN: 1286-4579 [Print] France |
PMID | 11580973
(Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Glucans
- Ligands
- NF-kappa B
- Polysaccharides
- Receptors, Immunologic
- beta-glucan receptor
- laminaran
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Topics |
- Animals
- Binding Sites
- Dose-Response Relationship, Drug
- Glucans
(metabolism)
- Humans
- Ligands
- Male
- Mice
- Mice, Hairless
- Mice, Inbred ICR
- Monocytes
(drug effects, metabolism)
- NF-kappa B
(metabolism)
- Polysaccharides
(immunology, metabolism, pharmacology)
- Protein Binding
- Receptors, Immunologic
(drug effects, metabolism)
- Sepsis
(immunology)
- U937 Cells
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