Granulocyte macrophage colony–stimulating factor is required for cytokine induction by a highly 6-branched 1,3-β-d-glucan fromAureobasidium pullulansin mouse-derived splenocytes

Abstract

We have previously obtained and elucidated the precise structure of a highly branched 1,3-β-D-glucan (with 6-monoglucopyranosyl side chains), Aureobasidium pullulans-fermented β-D-glucan (AP-FBG), from the fungus A. pullulans. However, the mechanism(s) of the effects of AP-FBG on in vitro mouse primary cells have not been analyzed in detail. Herein, we report that the induction of cytokines by AP-FBG was dependent on the existence of a granulocyte macrophage colony-stimulating factor (GM-CSF); this is similar way to be a typical 1,3-β-D-glucan from Sparassis crispa (SCG), which is a 1,3-β-D-glucopyranosyl backbone with single 1,6-β-D-glucopyranosyl side branching units every three residues. In other words, the production of cytokines in DBA/2-mouse-derived splenocytes by AP-FBG was completely hampered by an anti-GM-CSF neutralizing monoclonal antibody. Furthermore, the addition of exogenous GM-CSF to C57BL/6-derived splenocytes, which are less sensitive to AP-FBG, induced the production of cytokines by AP-FBG. Therefore, GM-CSF is indispensable for the induction of cytokines by AP-FBG in mouse-derived splenocytes. This finding has provided a new insight into our understanding of the actions of β-D-glucan but will also aid in the design and development of more effective β-D-glucan agents.

The Effect of Enzymatically Polymerised Polyphenols on CD4 Binding and Cytokine Production in Murine Splenocytes

“…The fruiting body of an edible Basidiomycetes mushroom, A. brasiliensis , rich in β-glucan induces NK cell activation through an IFN-γ-dependent pathway [23], [35]. Moreover, research has revealed that GM-CSF is required for the immunoenhancing activities induced by fungal-derived β-glucans [36]–[38], and that this mushroom has polyphenol-related enzymes such as polyphenol oxidase, and peroxidase [39], [40]. These enzymes could catalyse the polymerisation of phenolic compounds and activate the innate immune system through IFN-γ and GM-CSF production.…”

Agaricus brasiliensis-derived β-glucans exert immunoenhancing effects via a dectin-1-dependent pathway

“…This observation suggested that this fraction may contribute to the NK activation caused by the intake of A. brasiliensis fruiting body, given that IFN-γ is a mediator of NK activity [7,8]. Furthermore, given that GM-CSF is now considered the most important factor for up-regulating the reactivity of immune cells to 1,3-β-glucan [28,29], we hypothesized that cytokine synthesis induced by the Agaricus extracts may be due to their 1,3-β-glucan content. 1,3-β-Glucan is reported to be recognized by dectin-1, complement receptor type 3 (CR3), and lactosylceramide (LacCer) [30][31][32].…”

“…In general, soluble 1,3-β-glucans do not induce abundant cytokine production in C57BL/6 mice splenocytes without exogenous GM-CSF [28,29]. Indeed, the Agaricus extracts also did not activate naïve splenocytes (Fig.…”

Natural Products and Biological Activity of the Pharmacologically Active Cauliflower MushroomSparassis crispa

“…Harada et al further demonstrated that GM-CSF was one of the key factors in reactivity to SCG in DBA/2 mice [15, 17]. Neutralizing GM-CSF using an anti-GM-CSF monoclonal antibody significantly inhibited IFN- γ , TNF- α , and IL-12p70 elicited by SCG.…”

“…There is still little scientific evidence to explain the differences in responsiveness to beta-glucan in humans. The studies of differences in reactivity to SCG in different animal strains [14, 15, 17] are important from this viewpoint. Furthermore, it is interesting that agents such as CY can control reactivity to SCG, as well as the expression of various cytokines [26].…”