Inflammatory and immunopharmacological activities of meta-periodate oxidized zymosan

Zymosan (ZYM), a strong complement-activating yeast cell preparation compos ed mainly of mannan and beta-glucan moieties, is a potent inflammatory subs tance with immunopharmacological activity. We previously analyzed the metab olism of ZYM in mice and found that it was deposited in liver and spleen fo r at least several months and then gradually oxidatively degraded. In this paper, we prepared oxidized ZYM by sodium metaperiodate oxidation (NaIO4) a nd borohydride reduction (I/B-ZYM) and/or limited hydrolysis of oxidized mo ieties (I/B/H-ZYM). Activities of the resulting prod ucts 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) fo r H2O2 synthesis were concomi tantly solubilized by sonication of I/B/H-ZYM . On the countrary, TNF-alpha. production induced by I/B/H-ZYM was comparab le 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 imp ortant for biological activity of ZYM. Further, the minimal structure in ZY M necessary for biological activity may depend on the activity tested.