The influence of glucan polymer structure and solution conformation on binding to (1->3)- -D-glucan receptors in a human monocyte-like cell line

Abstract

Glucans are (1-3)-beta-D-linked polymers of glucose that are produced as fungal cell wall constituents and are also released into the extracellular milieu. Glucans modulate immune function via macrophage participation. The first step in macrophage activation by (1-3)-beta-D-glucans is thought to be the binding of the polymer to specific macrophage receptors. We examined the binding/uptake of a variety of water soluble (1-3)-beta-D-glucans and control polymers with different physicochemical properties to investigate the relationship between polymer structure and receptor binding in the CR3- human promonocytic cell line, U937. We observed that the U937 receptors were specific for (1-->3)-beta-D-glucan binding, since mannan, dextran, or barley glucan did not bind. Scleroglucan exhibited the highest binding affinity with an IC(50)of 23 nM, three orders of magnitude greater than the other (1-->3)-beta-D-glucan polymers examined. The rank order competitive binding affinities for the glucan polymers were scleroglucan>>>schizophyllan > laminarin > glucan phosphate > glucan sulfate. Scleroglucan also exhibited a triple helical solution structure (nu = 1.82, beta = 0.8). There were two different binding/uptake sites on U937 cells. Glucan phosphate and schizophyllan interacted nonselectively with the two sites. Scleroglucan and glucan sulfate interacted preferentially with one site, while laminarin interacted preferentially with the other site. These data indicate that U937 cells have at least two non-CR3 receptor(s) which specifically interact with (1-->3)-beta-D-glucans and that the triple helical solution conformation, molecular weight and charge of the glucan polymer may be important determinants in receptor ligand interaction.

Potentiating Effect of .BETA.-Glucans on Photodynamic Therapy of Implanted Cancer Cells in Mice

“…Therefore, it supports an idea, which was noted by Mueller et al (2000) that branching frequency may enhance the affinity of the polymer for the glucan receptor, and a polymer with greater molecular weight exhibits higher binding affinity. In addition, larger molecular weight β -glucans are absorbed more rapidly from the intestinal tract (Rice et al 2005), which can cause higher concentration of the substance at the tumor site.…”

Exposition of antitumour activity of a chemically characterized exopolysaccharide from a probiotic Lactobacillus plantarum MTCC 9510

“…β-Glucans (with the 1,3-linkage having substitution at C-2) producer lactic acid bacteria belonging to the Lactobacillus and Pediococcus genera are able to immunomodulate macrophages in vitro (Fernandez de Palencia et al 2009;Garai-Ibabe et al 2010). Differences in bioactivity may be due to differences in receptor affinity or receptor-ligand interaction on the cell surface (Mueller et al 2000). The present study unveils the therapeutic properties of the EPS produced by Lactobacillus plantarum MTCC 9510 and its relation to the elucidated structure.…”

The human β‐glucan receptor is widely expressed and functionally equivalent to murine Dectin‐1 on primary cells

“…The activity of bGR has been described on a variety of human leukocytes including monocytes [17], macrophages [18], eosinophils [19], neutrophils [20] and NK cells [21], and we had previously detected bGR mRNA in some of these cell populations [10]. To demonstrate the presence of this receptor on these cells, we examined surface expression of bGR on human PBL by flow cytometry, using GE2 to detect both major functional bGR isoforms.…”