Anti-infective effect of poly-beta 1-6-glucotriosyl-beta 1-3-glucopyranose glucan in vivo.

Department of Pathology, Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts.
Infection and Immunity (Impact Factor: 4.16). 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.


Available from: Gary R Ostroff, Jul 16, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The transition from late gestation to early lactation is characterized by substantial metabolic stress and altered immune function. The objective of this study was to assess the effects of supplementing a yeast product derived from Saccharomyces cerevisiae on immunity and uterine inflammation in transition cows. Forty multiparous Holstein cows were blocked by expected parturition date and randomly assigned within block to 1 of 4 treatments (n = 10) from 21 d before expected parturition to 42 d postpartum. Rations were top-dressed with a product containing yeast culture plus enzymatically hydrolyzed yeast (YC-EHY; Celmanax, Vi-COR, Mason City, IA) at the rate of 0, 30, 60, or 90 g/d throughout the experiment. Cows were injected subcutaneously with ovalbumin on d -21, -7, and 14 to assess their humoral response. Data were analyzed using mixed models with repeated measures over time. Concentrations of colostrum IgG were unaffected by treatments. A treatment × week interaction was observed for somatic cell linear score, reflecting a tendency for a quadratic dose effect on wk 1 (2.34, 2.85, 1.47, and 4.06 ± 0.59 for 0, 30, 60, and 90 g/d, respectively) and a quadratic dose effect on wk 5 (1.36, -0.15, -1.07, and 0.35 ± 0.64 for 0, 30, 60, and 90 g/d, respectively). Platelet count was increased by YC-EHY. Increasing YC-EHY dose linearly increased plasma anti-ovalbumin IgG levels following 3 ovalbumin challenges, suggesting that treatments enhanced humoral immunity. Increasing YC-EHY dose also quadratically increased fecal IgA concentrations in early lactation, suggesting that 30- and 60-g/d doses enhanced mucosal immunity. Uterine neutrophil populations were much greater in samples collected on d 7 compared with those on d 42 (32.1 vs. 7.6 ± 3.5% of cells), reflecting neutrophil infiltration immediately after calving, but no treatment effect was detected. Significant day effects were detected for mRNA of IL-6, IL-8, neutrophil myeloperoxidase (MPO), and neutrophil elastase (ELANE) in the uterine samples, reflecting greater abundance of these transcripts collected on d 7 compared with d 42. A quadratic dose effect was detected for IL-6, indicating that 30 and 60 g/d doses decreased uterine IL-6 mRNA. The mRNA abundance of MPO and ELANE was increased linearly by YC-EHY. Supplementation with YC-EHY enhanced measures of humoral and mucosal immunity and modulated uterine inflammatory signals and mammary gland health in transition dairy cows. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Migration of neutrophils requires sequential adhesive and deadhesive interactions between β1 and β2 integrins and components of the extracellular matrix. Prompted by reports that describe interaction of soluble β-glucan with the β2 integrin Mac-1, a role for β-glucan in regulation of integrin-mediated migration was investigated. Neutrophil migration in response to fMLP was assessed using an agarose overlay method with slides precoated with fibronectin (Fn) ± β-glucan. On Fn, random migration in excess of directed migration was observed. In contrast, migration on Fn + β-glucan was directional, with marked diminution of random migration. This conversion of random to directed migration was seen neither when Fn was supplemented with alternative polysaccharides nor when β-glucan was applied to other components of the extracellular matrix. This effect of β-glucan was shown to be cation dependent and to be effected by Arg-Gly-Asp-containing peptides consistent with an integrin-mediated event. mAb inhibition studies demonstrate that β-glucan effects this shift toward directed migration through suppression of migration mediated by Mac-1 and very late Ag 5 and enhancement of very late Ag 3-mediated migration. Adhesion assays suggest that the prochemotactic influence of β-glucan is due, in part but not entirely, to modulation of PMN adhesion to Fn. In summary, these data support a novel role for β-glucan in regulation of β1- and β2-mediated neutrophil migration on Fn.
    The Journal of Immunology 06/1999; 162(11):6792-6799. · 5.36 Impact Factor
  • Source
    [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 · 0.84 Impact Factor