A comparative evaluation of particulate and soluble glucan in an endotoxin model.
Particulate glucan (P) but not soluble glucan (F) has been shown to sensitize rats to endotoxins. This phenomenon is believed to be mediated by the reticuloendothelial system (RES). The effect of glucan-P and -F on the RES, and the response of glucan-treated rats to nonlethal doses of endotoxin were investigated. Rats were injected for 5 days with 10 mg/kg of glucan-P, -F or saline. Three days later rats were either (1) injected with colloidal carbon for clearance studies, (2) sacrificed for organ histology and determination of serum glucose, plasma thromboxane (Tx) B2, and plasma 6-keto-prostaglandin (PG) F1 alpha concentrations, or (3) challenged with a nonlethal dose of endotoxin. The latter were further subdivided into groups for either 30-day survival or for sacrifice at 30 min or 4 h post-endotoxin infusion to obtain blood samples for glucose, TxB2, and 6-keto-PGE1 alpha determinations. Glucan-P induced hepatosplenomegaly and granulomatous changes within the liver and spleen. The carbon clearance halftime was markedly decreased in these animals. In glucan-P-treated rats challenged with endotoxin, elevated concentrations of both plasma prostanoids were observed as well as alterations in serum glucose levels. These changes were less pronounced in glucan-F- or saline- treated rats. Following endotoxin challenge, only 40% of glucan-P-treated rats survived 30 days whereas 100% of both the glucan-F and saline-treated rats survived. We conclude that glucan-P, in contrast to glucan-F, significantly heightens RES function and that this effect likely accounts for the endotoxin sensitivity.
D000818:Animals; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli / Q000276:immunology; D005936:Glucans / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013329:Structure-Activity Relationship
D004731:Endotoxins; D005936:Glucans; D008070:Lipopolysaccharides