We have studied the effect of glucan, a potent immunomodulating agent with immunotherapeutic potential for man, on murine natural killer (NK) cells. The results of our experiments have shown that a single i.v. injection of 4 mg of glucan caused significant depression of NK cell activities residing in the bone marrow and spleens of B6DF1 mice. The depression of NK cell cytotoxicity was expressed 24 hr after glucan treatment and lasted as long as the mice were tested, i.e., 15 days after treatment. Impairment of NK cell functions caused by glucan could not be mediated via mature T cell functions since the congenitally athymic BALB/c mice were also hyporeactive after glucan injection. The negative effect of glucan on NK cells is disturbing if one considers NK cells as an important component in immunosurveillance and in immunity to malignancies.

In order to test the relationship between NK cell and bone marrow effector (BM-E) cells, which can represent the same cell population(s) or subpopulation(s), we have studied also the effect of glucan on bone marrow graft rejection potential in B6DF1 mice. Bone marrow transplantation studies have shown close correlation between NK cell and BM-E cell activities. Specifically, at the time when glucan caused depression of NK cell anti-tumor activities (i.e., on days 2, 6, 11, and 15 after injection), there was also a prevention of rejection of histo-incompatible bone marrow transplants, and vice versa, histoincompatible bone marrow grafts were always rejected by untreated B6DF1 mice expressing high degree of NK cell anti-tumor activities. These results indicate, further, the similarity between NK cell and BM-E cells and, moreover, suggest possible benefits of glucan in bone marrow transplantation.

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This work was supported by Grants CA 21062 from National Cancer Institute and IN-121 from the American Cancer Society.

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