Signal Transduction Pathway on β-Glucans-Triggered Hydrogen Peroxide Production by Murine Peritoneal Macrophages in Vitro

Abstract

It has been reported that the biological activities of several β-glucans vary due to differences in their physicochemical properties. In this study we investigated the ability of β-glucans to trigger H₂O₂ production and activate signaling pathway on peritoneal macrophages. The most effective β-glucan tested on H₂O₂ production was zymocel which was a particulate preparation from the yeast cell wall. In contrast, gel-forming β-glucans which are known as immunoenhancers did not trigger the H₂O₂ production by macrophages at all. To identify the related signaling pathway for the particulate β-glucans-triggered H₂O₂ production, several inhibitors were applied. Hydrogen peroxide production triggered with phorbol myristate acetate was inhibited by pretreatment of macrophages with H-7, a protein kinase C inhibitor. However, β-glucans-triggered H₂O₂ production was not affected by H-7. The results suggested that genistein-sensitive tyrosine kinase and bromophenacyl bromide-sensitive phospholipase A₂ participated in the particulate β-glucans-triggered H₂O₂ production, although the phagocytosis of particulate β-glucans was not inhibited by either reagents. In conclusion, gel-forming (1→3)-β-D-glucans-induced activation was not sufficient to trigger H₂O₂ on macrophages, and pathways for particulate β-glucans-triggered H₂O₂ production were regulated differently from those for phagocytosis of β-glucans.