Abstract
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.
Footnotes
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This work was supported, in part, by Public Health Service Grants GM53522 from the National Institute of General Medical Sciences, AI45829 from the National Institute of Allergy and Immunology, and AT00501 from the National Center for Complementary and Alternative Medicine (to D.L.W.). No corporate or commercial support was received for these studies.
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doi:10.1124/jpet.105.085415.
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ABBREVIATIONS: FDA, Food and Drug Administration; IL, interleukin; GI, gastrointestinal; DAP, diaminopropane; PBS, phosphate-buffered saline; GALT, gut-associated lymphoid tissue; FITC, fluorescein isothiocyanate; TLR, toll-like receptor.
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↵1 Current address: Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
- Received February 25, 2005.
- Accepted June 6, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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