Glucan and immunotoxicity
International Clinical Pathology Journal
Some interesting experiments have shown that glucans of different sources have a strong protective ability against different mutagenic agents such as 22-aminoanthracene or methyl methyanesulfonate. In these studies, glucans protected the cells by sheltering their DNA and effectively increasing the repair of the double-strand breaks. These studies were further confirmed by findings showing the efficacy of glucan in reducing the damage caused by other mutagenic agents such as doxorubicin,
... oxorubicin, cisplatin, cyclophosphamide and adriamycin. Some of the effects of glucans are attributed to their ability to trap free radicals which are produced during the biotransformation of these chemotherapeutic drugs. In addition, glucan supports the mitotic activity of bone marrow cells, 1 which further helps to overcome the negative biological effects of anti-neoplastic drugs. Additional possible effects of glucan on bone marrow cells might be enhancement of the viability of bone marrow cells (shown as increase in bone marrow CFU-GM colony formation and by direct cytotoxocity tests) leading to protection against doxorubicin-induced toxicity. This is particularly important in clinical practice, since myelotoxic injury to the bone marrow is a severe consequence to either total body irradiation or massive chemotherapeutic treatment. The role of glucan in reduction of toxic effects of irradiation/chemotherapy was often explained by the increase of proliferation of bone marrow stem cells. However, direct evidence of this was either missing or completely overlooked. A recent study focused on deposition of iC3b on bone marrow stroma cells and on the interaction of these cells with hematopoietic progenitor cells. The study showed that stroma-iC3b tethers progenitor cells via inserted I-domain of the complement receptor 3 expressed on progenitor cells. The addition of glucan can cause changes in proliferation of tethered progenitor cells with subsequent activation of leukocyte recovery 2 leading to either faster recovery or higher survival rate observed by many in models including mice and pigs. This hypothesis was further documented by showing that better survival of irradiated animals after transplantation of hematopoietic progenitor cells is CR3-dependent. These findings represent not only a different view on glucan effecting bone marrow, but also on its new role in activating tissue repair. In addition to bone marrow recovery, glucan has also been found to possess some protective effects against electromagnetic radiation. A recent study using a model of 2.45 GHz electromagnetic radiation and possible oxidative injury of the skin demonstrated oral administration of glucan before the radiation reversed the increase in MDA levels and decrease in SOD activities caused by radiation. Based on these data, authors concluded that orally-given glucan can offer protection against oxidative injury induced by electromagnetic radiation, most probably through its anti-oxidant abilities. 3 These abilities to trap free radicals including singlet oxygen and hydroxyl radical are well established. Glucan was also tested in the case of mercury poisoning. Global mercury recycling resulted in a significant presence of mercury salts in the environment, with the fish industry being hit particularly hard. In addition, thimerosal (containing an organic ethylmercury), still represent a substance with dangerous immunosuppressive effects. Other mercury salts also possess immunosuppressive and toxic properties. A more detailed study showed that two week exposure of mice to either thimerosal or mercury acetate in drinking water caused significant suppression of humoral and cellular immune reactions such as antibody response, cytokine secretion, phagocytosis, cell proliferation and natural killer activity. However, a two-week feeding with yeast-derived insoluble glucan resulted in significantly lower immunosuppressive effects of mercury. 4 The mechanisms by which glucan administration blocks or at least lowers mercury-mediated immunosuppression are currently unclear. In addition to plain stimulation of immune reactions, which supplements lower immunity caused by mercury exposure, one can speculate about the activation of some immunologically important genes or about limitation of inflammation and oxidative stress. Another study focused on glucan's ability to reverse the immunosuppression caused by immunotoxic agents. These experiments used perfluorinated compounds, namely perfluooctane sulphonic acid and perluorooctanic acid, which are bioaccumulative chemicals present in thousands of products. With their known long lifetime in the environment, it is not surprising that these products were detected in the blood of both animals and humans. A human study later showed a decrease in humoral immunity as a result of immunization was caused by heavy exposure to these compounds. Various animal models showed suppression of natural killer cell activity and cell proliferation, suppression of humoral immunity and inhibition of T and IL-6 and IL-10 secretion. Our laboratory sought information to determine if glucan can help to reduce the immunotoxic effects of these compounds. Our studies showed that oral exposure to perfluooctane sulphonic acid or perluorooctanic acid resulted in severe immunosuppression, tested by natural killer cell activity, phagocytosis, cell proliferation and antibody response. Most of this suppression was, however, reduced by an oral administration of the glucan. Editorial For decades, glucan has been shown to help overcome the immunosuppressive effects of numerous factors, including chemotherapy and irradiation. Recent studies suggesting a possible new function for glucan have emerged. Not surprisingly, these studies are based on the well-established fact that glucan strongly stimulates all facets of immune response, from nonspecific response to cellular and humoral responses. From this knowledge came the presumption that glucan might be able to overcome or at least lower some immunosuppression caused by toxic agents.