The cytokine stimulating activity of (1-->3)-beta-D-glucans is dependent on the triple helix conformation.
The immunomodulating properties of comb-like branched (1-->3)-beta-D-glucans scleroglucan, schizophyllan and lentinan depend on branching pattern, molecular weight and higher-order structure. The effect of weight average molecular weight Mw and higher order structure of scleroglucan, on stimulation of human monocytes cultured in vitro to secrete tumor necrosis factor-alpha (TNF-alpha) was investigated. The higher order structures of the scleroglucan samples were determined by electron microscopy. The data showed that the samples with a linear wormlike, triple helical structure with Mw less than 50 x 10(4) g/mol or larger than 110 x 10(4) g/mol stimulated the monocytes more efficiently than samples with Mw in the range (67-110) x 10(4) g/mol. The denaturation of the linear triple helices by NaOH (> 0.25 M), followed by neutralization yielded blends of linear and macrocyclic topologies with concomitant irreversible reduction of the cytokine inducing activity compared with the untreated scleroglucans. The dose-dependent ability to activate monocytes to cytokine production was not restored following annealing of the denatured-renatured samples, despite the fact that electron micrographs revealed similar structures of these annealed samples to the starting material. Pre-incubation of monocytes with antibodies against cluster of differentiation antigens CD14 or CD11b reduced the scleroglucan potency to stimulate TNF-alpha secretion mainly for mAb against CD14 in the presence of serum.
Falch
B H
BH
Department of Physics, The Norwegian University of Science and Technology, Trondheim.
Espevik
T
T
Ryan
L
L
Stokke
B T
BT
D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology*; D002236:Carbohydrate Conformation; D016207:Cytokines / Q000096:biosynthesis*; D005936:Glucans / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007912:Lentinan / Q000737:chemistry / Q000494:pharmacology; D008970:Molecular Weight; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D012566:Sizofiran / Q000737:chemistry / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D016207:Cytokines; D005936:Glucans; D014409:Tumor Necrosis Factor-alpha; D007912:Lentinan; C045938:scleroglucan; D012566:Sizofiran