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 Kd of 31 μM (95% CI 20-48 μM) and 100% inhibition. However, the glucan heptasaccharide did not stimulate U937 monocyte NFκB signaling, nor did it increase survival in a murine model of polymicrobial sepsis. Laminarin, a larger and more complex glucan polymer (Mw=7700 g/mol), only partially inhibited binding (61±4%) at a Kd of 2.6 μM (99% CI 1.7-4.2 μM) 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 NFκB-dependent signaling pathways or protection against experimental sepsis.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-20432 |
| Date | 01 January 2001 |
| Creators | Lowe, Elizabeth, Rice, Peter, Ha, Tuanzhu, Li, Chuanfu, Kelley, Jim, Ensley, Harry, Lopez-Perez, Jose, Kalbfleisch, John, Lowman, Douglas, Margl, Peter, Browder, William, Williams, David |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | ETSU Faculty Works |
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