Signal transduction pathway on beta-glucans-triggered hydrogen peroxide production by murine peritoneal macrophages in vitro.
It has been reported that the biological activities of several beta-glucans vary due to differences in their physicochemical properties. In this study we investigated the ability of beta-glucans to trigger H2O2 production and activate signaling pathway on peritoneal macrophages. The most effective beta-glucan tested on H2O2 production was zymocel which was a particulate preparation from the yeast cell wall. In contrast, gel-forming beta-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 beta-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, beta-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 beta-glucans-triggered H2O2 production, although the phagocytosis of particulate beta-glucans was not inhibited by either reagents. In conclusion, gel-forming (1-->3)-beta-D-glucans-induced activation was not sufficient to trigger H2O2 on macrophages, and pathways for particulate beta-glucans-triggered H2O2 production were regulated differently from those for phagocytosis of beta-glucans.
Okazaki
M
M
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Chiba
N
N
Adachi
Y
Y
Ohno
N
N
Yadomae
T
T
D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors; D005936:Glucans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010587:Phagocytosis / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002147:Calmodulin; D005936:Glucans; D006861:Hydrogen Peroxide; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate