Relationship between structure and immunostimulating activity of enzymatically synthesized glycogen

Glycogen acts as energy and carbon reserves in animal cells and in microorganisms. Although anti-tumor activity has recently been reported for shellfish glycogen and enzymatically synthesized glycogen, the activity of glycogen has not yet been fully clarified. We enzymatically prepared various sizes of glycogens with controlled structures to investigate the relationship between the structure and immunostimulating activity of glycogen. The results revealed that glycogens with a weight-average molecular weight (Mw) of more than 10,000K hardly activated RAW264.7, a murine macrophage cell line, whereas glycogens of Mw 5000K and 6500K strongly stimulated RAW264.7 in the presence of interferon-gamma (IFN-γ), leading to augmented production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Comparing the fine structure of the glycogens, the average-number of chain length, as well as the exterior and the interior chain lengths of the glycogens, had minor correlation between active and less-active glycogen derivatives. The available evidence suggests that the macrophage-stimulating activity of glycogen is strictly related to its molecular weight rather than to any fine structural property.

Graphical abstractWe established the fact that the molecular weight (5000–6500K) of glycogen is closely related to macrophage stimulation and augments the production of NO, TNF-α, and IL-6. The fine structure of the glycogen has a minor correlation with macrophage stimulation. Some experimental results indicate that the macrophage-stimulating mechanism of glycogen differs from that of LPS.