Rice Peter J, Adams Elizabeth L, Ozment-Skelton Tammy, Gonzalez Andres J, Goldman Matthew P, Lockhart Brent E, Barker Luke A, Breuel Kevin F, Deponti Warren K, Kalbfleisch John H, Ensley Harry E, Brown Gordon D, Gordon Siamon, Williams David L
Department of Pharmacology, East Tennessee State University, Johnson City, TN 37614, USA.
J Pharmacol Exp Ther. 2005 Sep;314(3):1079-86. doi: 10.1124/jpet.105.085415. Epub 2005 Jun 23.
Glucans are immunomodulatory carbohydrates found in the cell walls of fungi and certain bacteria. We examined the pharmacokinetics of three water-soluble glucans (glucan phosphate, laminarin, and scleroglucan) after oral administration of 1 mg/kg doses in rats. Maximum plasma concentrations for glucan phosphate occurred at 4 h. In contrast, laminarin and scleroglucan showed two plasma peaks between 0.5 and 12 h. At 24 h, 27 +/- 3% of the glucan phosphate and 20 +/- 7% of the laminarin remained in the serum. Scleroglucan was rapidly absorbed and eliminated. The liver did not significantly contribute to the clearance of plasma glucan. Biological effects were further studied in mice. Following oral administration of 1 mg, glucans were bound and internalized by intestinal epithelial cells and gut-associated lymphoid tissue (GALT) cells. Internalization of glucan by intestinal epithelial cells was not Dectin-dependent. GALT expression of Dectin-1 and toll-like receptor (TLR) 2, but not TLR4, increased following oral administration of glucan. Oral glucan increased systemic levels of interleukin (IL)-12 (151 +/- 15%) in mice. Oral glucan administration also increased survival in mice challenged with Staphylococcus aureus or Candida albicans. These data demonstrate that orally administered water-soluble glucans translocate from the gastrointestinal (GI) tract into the systemic circulation. The glucans are bound by GI epithelial and GALT cells, and they modulate the expression of pattern recognition receptors in the GALT, increase IL-12 expression, and induce protection against infectious challenge.
葡聚糖是存在于真菌和某些细菌细胞壁中的免疫调节性碳水化合物。我们在大鼠口服1mg/kg剂量的三种水溶性葡聚糖（磷酸葡聚糖、海带多糖和硬葡聚糖）后检测了它们的药代动力学。磷酸葡聚糖的最大血浆浓度出现在4小时。相比之下，海带多糖和硬葡聚糖在0.5至12小时之间出现两个血浆峰。在24小时时，血清中仍保留27±3%的磷酸葡聚糖和20±7%的海带多糖。硬葡聚糖吸收和消除迅速。肝脏对血浆葡聚糖的清除没有显著贡献。在小鼠中进一步研究了其生物学效应。口服1mg葡聚糖后，葡聚糖被肠道上皮细胞和肠道相关淋巴组织（GALT）细胞结合并内化。肠道上皮细胞对葡聚糖的内化不依赖于脱铁素。口服葡聚糖后，GALT中脱铁素-1和Toll样受体（TLR）2而非TLR4的表达增加。口服葡聚糖可提高小鼠体内白细胞介素（IL）-12的全身水平（151±15%）。口服葡聚糖还可提高感染金黄色葡萄球菌或白色念珠菌的小鼠的存活率。这些数据表明，口服的水溶性葡聚糖可从胃肠道（GI）转运至体循环。葡聚糖被GI上皮细胞和GALT细胞结合，并调节GALT中模式识别受体的表达，增加IL-12的表达，并诱导对感染性挑战的保护作用。
