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

Glucans are (1-3)-beta-D-linked polymers of glucose that are produced as fu ngal cell wall constituents and are also released into the extracellular mi lieu. Glucans modulate immune function via macrophage participation. The fi rst 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 th e, binding/uptake of a variety of water soluble (1-3)-beta-D-glucans and co ntrol polymers with different physicochemical properties to investigate the relationship between polymer structure End receptor binding in the CR3- hu man promonocytic cell line, U937, We observed that the U937 receptors were specific for (1-->3)-beta-D-glucan binding, since mannan, dextran, or barle y glucan did not bind. Scleroglucan exhibited the highest binding affinity with an IC50 of 23 nM, three orders of magnitude greater than the other (1- ->3)-beta-D-glucan polymers examined, The rank order competitive binding af finities for the glucan polymers were scleroglucan>>>schizophyllan > lamina rin > glucan phosphate > glucan sulfate, Scleroglucan also exhibited a trip le helical solution structure (v = 1.82, beta = 0.8), There were two differ ent binding/uptake sites on U937 cells. Glucan phosphate and schizophyllan interacted nonselectively with the two sites. Scleroglucan and glucan sulfa te interacted preferentially with one site, while laminarin interacted pref erentially with the other site. These data indicate that U937 cells have at least two non-CR3 receptor(s) which specifically interact with (1-->3)-bet a-D-glucans and that the triple helical solution conformation, molecular we ight and charge of the glucan polymer may be important determinants in rece ptor ligand interaction.