Anti-infective effect of poly-β1-6-glucotriosyl-β1-3-glucopyranose glucan in vivo

Department of Pathology, Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts.
Infection and Immunity (Impact Factor: 3.73). 05/1992; 60(4):1642-7.
Source: PubMed

ABSTRACT Mice challenged with Escherichia coli or Staphylococcus aureus were protected against lethal peritonitis by the intravenous administration of 10 micrograms of poly-beta 1-6-glucotriosyl-beta 1-3-glucopyranose (PGG) glucan per animal 4 to 6 h prior to bacterial challenge. Subsequent studies with the rat model for intra-abdominal sepsis indicated that intramuscular doses of 10 to 100 micrograms per animal 24 and 4 h prior to surgical implantation of the bacterial inoculum reduced the early mortality associated with the peritonitis phase of this experimental disease process. Quantitative cultures of blood obtained from challenged rats showed that significantly fewer organisms were present in the blood of PGG glucan-treated animals than in that of untreated animals. Quantitative studies of leukocytes of rats and mice following a single injection of PGG glucan showed a modest transient increase in the total leukocyte count. The possible mechanisms by which protection occurs in the animal model system are discussed.

Download full-text


Available from: Gary R Ostroff, Jul 16, 2014
7 Reads
  • Source
    • "Neutrophils obtained from glucan-treated mice showed enhanced phagocytosis of E. coli in ex vivo experiments (63). In vivo administration of poly-[1-6]-β-D-glucopyranosyl-[1–3]-β-D-glucopyranose (PGG-glucan) in rats before bacterial challenge increased the number of leukocytes and also protected against lethal peritonitis (64). Similarly, in a mouse model of dental infection, PGG-glucan reduced infection-stimulated periapical bone resorption (65). "
    [Show abstract] [Hide abstract]
    ABSTRACT: New foods and natural biological modulators have recently become of scientific interest in the investigation of the value of traditional medical therapeutics. Glucans have an important part in this renewed interest. These fungal wall components are claimed to be useful for various medical purposes and they are obtained from medicinal mushrooms commonly used in traditional Oriental medicine. The immunotherapeutic properties of fungi extracts have been reported, including the enhancement of anticancer immunity responses. These properties are principally related to the stimulation of cells of the innate immune system. The discovery of specific receptors for glucans on dendritic cells (dectin-1), as well as interactions with other receptors, mainly expressed by innate immune cells (e.g., Toll-like receptors, complement receptor-3), have raised new attention toward these products as suitable therapeutic agents. We briefly review the characteristics of the glucans from mycelial walls as modulators of the immunity and their possible use as antitumor treatments.
    International Journal of Oncology 06/2013; 43(2). DOI:10.3892/ijo.2013.1974 · 3.03 Impact Factor
  • Source
    • "Among the various β(1,3), β(1,4), and β(1,6) β-glucan linkages, only β(1,3) stimulates immunity and shows antitumor activities. The first reported major function of β-glucans was antitumor activity (Chihara et al., 1970); since then, many other biological activities have been reported, including antifungal, anti-infection (Onderdonk et al., 1992), radioprotective (Gu et al., 2005), cholesterol reduction (Wolever et al., 2011), and postprandial glucose metabolic activities (Battilana et al., 2001). β-Glucans have been used in prophylactic applications for their immunopotentiation activity as vaccine or adjuvant candidates against Aspergillus (Torosantucci et al., 2005) and Candida vaginal (Pietrella et al., 2010) infections in animals, and against Vibrio infection in marine fish (Zhu et al., 2006). "
    [Show abstract] [Hide abstract]
    ABSTRACT: During the course of evolution, animals encountered the harmful effects of fungi, which are strong pathogens. Therefore, they have developed powerful mechanisms to protect themselves against these fungal invaders. β-Glucans are glucose polymers of a linear β(1,3)-glucan backbone with β(1,6)-linked side chains. The immunostimulatory and antitumor activities of β-glucans have been reported; however, their mechanisms have only begun to be elucidated. Fungal and particulate β-glucans, despite their large size, can be taken up by the M cells of Peyer's patches, and interact with macrophages or dendritic cells (DCs) and activate systemic immune responses to overcome the fungal infection. The sampled β-glucans function as pathogen-associated molecular patterns (PAMPs) and are recognized by pattern recognition receptors (PRRs) on innate immune cells. Dectin-1 receptor systems have been incorporated as the PRRs of β-glucans in the innate immune cells of higher animal systems, which function on the front line against fungal infection, and have been exploited in cancer treatments to enhance systemic immune function. Dectin-1 on macrophages and DCs performs dual functions: internalization of β-glucan-containing particles and transmittance of its signals into the nucleus. This review will depict in detail how the physicochemical nature of β-glucan contributes to its immunostimulating effect in hosts and the potential uses of β-glucan by elucidating the dectin-1 signal transduction pathway. The elucidation of β-glucan and its signaling pathway will undoubtedly open a new research area on its potential therapeutic applications, including as immunostimulants for antifungal and anti-cancer regimens.
    Biomolecules and Therapeutics 09/2012; 20(5):433-445. DOI:10.4062/biomolther.2012.20.5.433 · 1.73 Impact Factor
    • "Onderdonk et al. found that mice challenged with E. coli or S. aureus bacteria are protected against septic infections when they are injected with PGG-glucan four to six hours prior to infection. Additional research further supports that yeast β-glucan reduces septic shock by killing bacteria present in blood.[50] A study by Kernodle et al. has demonstrated that preventative dosing of yeast β-glucan, prior to infection with S. aureus, prevented sepsis in a guinea pig model. "
    [Show abstract] [Hide abstract]
    ABSTRACT: β-Glucans are soluble fibers with physiological functions, such as, interference with absorption of sugars and reduction of serum lipid levels. β-glucans are found in different species, such as, Rhynchelytrum repens, Lentinus edodes, Grifola frondosa, Tremella mesenterica, Tremella aurantia, Zea may, Agaricus blazei, Phellinus baummi, Saccharomyces cerevisae (yeast), and Agaricus blazei murell (mushroom). Analysis of the fractions reveals the presence of arabinose, glucose, xylose, and traces of rhamnose and galactose. The presence of β-glucan in these fractions is confirmed by hydrolyzing the polymers with endo-β-glucanase from Bacillus subtilis, followed by high-performance liquid chromatography (HPLC) analysis of the characteristic oligosaccharides produced. The 4 M KOH fractions from different tissues are subjected to gel permeation chromatography on Sepharose 4B, with separation of polysaccharides, with different degrees of polymerization, the highest molecular mass (above 2000 kDa) being found in young leaves. The molecular mass of the leaf blade polymers is similar (250 kDa) to that of the maize coleoptiles β-glucan used for comparison. The 4 M KOH fraction injected into rats with streptozotocin-induced diabetes has shown hypoglycemic activity, reducing blood sugar to normal levels for approximately 24 hours. This performance is better than that obtained with pure β-glucan from barley, which decreases blood sugar levels for about four hours. These results suggest that the activity of β-glucans is responsible for the use of this plant extract as a hypoglycemic drug in folk medicine.
    Journal of Advanced Pharmaceutical Technology & Research 04/2011; 2(2):94-103. DOI:10.4103/2231-4040.82953
Show more