Inflammatory and immunopharmacological activities of meta-periodate oxidized zymosan

Zymosan (ZYM), a strong complement-activating yeast cell preparation composed mainly of mannan and beta-glucan moieties, is a potent inflammatory substance with immunopharmacological activity. We previously analyzed the metabolism of ZYM in mice and found that it was deposited in liver and spleen for at least several months and then gradually oxidatively degraded. In this paper, we prepared oxidized ZYM by sodium metaperiodate oxidation (NaIO4) and borohydride reduction (I/B-ZYM) and/or limited hydrolysis of oxidized moieties (I/B/H-ZYM). Activities of the resulting products were assessed by (i) vascular permeability in mice, (ii) H2O2 synthesis by macrophages, (iii) TNF-alpha synthesis by macrophages, and (iv) reactivity to anti-ZYM sera. As a general trend, NaIO4, oxidation products exhibited reduced, but still significant, activity. Interestingly, the H2O2 production induced by I/B/H-ZYM was significantly reduced after extensive sonication. Antagonist(s) for H2O2 synthesis were concomitantly solubilized by sonication of I/B/H-ZYM. On the contrary, TNF-alpha production induced by I/B/H-ZYM was comparable with that of ZYM. These facts strongly suggest that highly branched 1,3-beta- and 1,6-beta-glucosidic linkages resistant to NaIO4 oxidation are important for biological activity of ZYM. Further, the minimal structure in ZYM necessary for biological activity may depend on the activity tested.