Effect over time of in-vivo administration of the polysaccharide arabinogalactan on immune and hemopoietic cell lineages in murine spleen and bone marrow.

Current evidence indicates an immunostimulating role for complex carbohydrates, i.e., polysaccharides, from several plant sources. In the present work, we determined the specific in vivo effects, with time of administration, of one such compound, a neutral arabinogalactan from larch not only on immune (lymphoid) cells, but also on natural killer (NK) lymphoid cells, as well as a variety of other hemopoietic cells in both the bone marrow and spleen of healthy, young adult mice. The latter were injected daily (i.p.) with arabinogalactan (500 microg in 0.1 ml pH 7.2 phosphate buffered saline-PBS) for 7 or 14 days. Additional, aged (1 1/2-2 yr) mice were similarly injected for 14 days only. Control mice were given the PBS vehicle in all cases, following the above injection regimen. Animals from all groups were sampled 24 h after the final injection and the immune and hemopoietic cell populations in the bone marow and spleen were assessed quantitatively. The results indicated that immediately following either 7 or 14 days of arabinogalactan administration to young, adult mice, lymphoid cells in the bone marrow were significantly decreased (p < 0.004; p < 0.001, respectively) relative to controls but remained unchanged at both time intervals in the spleen. NK cells, after 7 days of arabinogalactan exposure, were also decreased significantly in the bone marrow (p < 0.02), but unchanged in the spleen. After 14 days' exposure to the polysaccharide, NK cells in the bone marrow had returned to normal (control) levels, but were increased in the spleen (p < 0.004) to levels greater than 2-fold that of control. Among other hemopoietic cell lineages, none was influenced in the bone marrow or spleen by one-week administration of arabinogalactan; however, after two-week exposure, precursor myeloid cells and their mature (functional) progeny (granulocytes), were significantly reduced in the spleen (p < 0.043; p < 0.006, respectively), as were splenic monocytes (p < 0.001). These lineages in the bone marrow, however, remained steadfastly unaltered even after 14 days of continuous exposure to the agent. Of the vast cascade of cytokines induced in the presence of this polysaccharide, it appears that immunopoiesis- and hemopoiesis-inhibiting ones are most prevalent during at least the first two weeks of daily exposure.

[1]  Sandra C. Miller,et al.  The effect of immunization with killed tumor cells, with/without feeding of Echinacea purpurea in an erythroleukemic mouse model. , 2002, Journal of alternative and complementary medicine.

[2]  S. Miller,et al.  Echinacea purpurea and melatonin augment natural-killer cells in leukemic mice and prolong life span. , 2001, Journal of alternative and complementary medicine.

[3]  Z. Franck,et al.  Immunopharmacological activity of Echinacea preparations following simulated digestion on murine macrophages and human peripheral blood mononuclear cells , 2000, Journal of leukocyte biology.

[4]  S. Miller,et al.  Natural killer cells from aging mice treated with extracts from Echinacea purpurea are quantitatively and functionally rejuvenated , 2000, Experimental Gerontology.

[5]  S. Miller,et al.  The American coneflower: a prophylactic role involving nonspecific immunity. , 1999, Journal of alternative and complementary medicine.

[6]  U. Edlund,et al.  Influence of polysaccharides from Viscum album L. on human lymphocytes, monocytes and granulocytes in vitro. , 1999, Anticancer research.

[7]  N. Currier,et al.  Natural Killer Cell Levels in Older Adult Mice Are Gender-Dependent: Thyroxin Is a Gender-Independent Natural Killer Cell Stimulant , 1999, Natural Immunity.

[8]  G. Kelly Larch arabinogalactan: clinical relevance of a novel immune-enhancing polysaccharide. , 1999, Alternative medicine review : a journal of clinical therapeutic.

[9]  N. Currier,et al.  Influence of an Interferon Inducer on Bone Marrow Transplant Reconstitution in Irradiated, Leukemic Mice: Elevated Natural Killer Cell Numbers and Improved Life Span , 1998, Natural Immunity.

[10]  S. Miller,et al.  Strain differences in natural killer cell-mediated immunity among mice: a possible mechanism for the low natural killer cell activity of A/J mice. , 1998, Immunobiology.

[11]  S. Miller,et al.  Effect on leukemia cell numbers of in vivo administration of immunotherapeutic agents is age-dependent. , 1996, Oncology.

[12]  R. Bauer [Echinacea drugs--effects and active ingredients]. , 1996, Zeitschrift fur arztliche Fortbildung.

[13]  I. Dussault,et al.  Decline in natural killer cell-mediated immunosurveillance in aging mice — a consequence of reduced cell production and tumor binding capacity , 1994, Mechanisms of Ageing and Development.

[14]  S. Miller The development of natural killer (NK) cells from Thy-1loLin-Sca-1+ stem cells: acquisition by NK cells in vivo of the homing receptor MEL-14 and the integrin Mac-1. , 1994, Immunobiology.

[15]  J. Cowdery,et al.  Interferon-γ Regulation of B Lymphocyte Differentiation: Activation of B Cells Is a Prerequisite for IFN-γ-Mediated Inhibition of B Cell Differentiation , 1994 .

[16]  R. Bauer,et al.  In Vitro Inhibition of Cyclooxygenase and 5-Lipoxygenase by Alkamides from Echinacea and Achillea Species , 1994, Planta medica.

[17]  M. Lohmann‐Matthes,et al.  Polysaccharides isolated from plant cell cultures of Echinacea purpurea enhance the resistance of immunosuppressed mice against systemic infections with Candida albicans and Listeria monocytogenes. , 1993, International journal of immunopharmacology.

[18]  S. Miller,et al.  Stimulation of natural killer cell numbers but not function in leukemic infant mice: a system primed in infancy allows survival in adulthood. , 1993, Natural immunity.

[19]  S. Miller Age-related differences in the effect of in vivo administration of indomethacin on hemopoietic cell lineages of the spleen and bone marrow of mice , 1992, Experientia.

[20]  H. Patel,et al.  Age‐associated changes in mitogen‐induced protein phosphorylation in murine T lymphocytes , 1992, European journal of immunology.

[21]  S. Miller,et al.  Population dynamics of natural killer cells in the spleen and bone marrow of normal and leukemic mice during in vivo exposure to interleukin-2. , 1991, Immunobiology.

[22]  K. Ishihara,et al.  A VCAM-like adhesion molecule on murine bone marrow stromal cells mediates binding of lymphocyte precursors in culture , 1991, The Journal of cell biology.

[23]  G. Butenko,et al.  Stromal hemopoietic microenvironment in aging , 1990, Mechanisms of Ageing and Development.

[24]  G. Gifford,et al.  Macrophage activation by the polysaccharide arabinogalactan isolated from plant cell cultures of Echinacea purpurea. , 1989, Journal of the National Cancer Institute.

[25]  S. Seremetis,et al.  Diversity in inhibitory effects of IFN-gamma and IFN-alpha A on the induced DNA synthesis of a hairy cell leukemia B lymphocyte clone reflects the nature of the activating ligand , 1988 .

[26]  N. Holbrook,et al.  Decreased proliferation, interleukin 2 synthesis, and interleukin 2 receptor expression are accompanied by decreased mRNA expression in phytohemagglutinin-stimulated cells from elderly donors. , 1988, The Journal of clinical investigation.

[27]  C. Rosse,et al.  The primary role of murine bone marrow in the production of natural killer cells. A cytokinetic study. , 1987, Journal of immunology.

[28]  J. Suttles,et al.  Evidence that expression of asialo-GM1 may be associated with cell activation. Correlation of asialo-GM1 expression with increased total cellular RNA and protein content in normal thymocyte and spleen cell populations. , 1987, Journal of immunology.

[29]  A. Abbas,et al.  Inhibition of B lymphocyte activation by interferon-gamma. , 1987, Journal of immunology.

[30]  D. G. Osmond,et al.  B lymphocyte progenitors in mouse bone marrow. , 1987, International reviews of immunology.

[31]  P Clark,et al.  Lymphocyte subsets in normal bone marrow. , 1986, Blood.

[32]  H. Vié,et al.  Decline, with age, in the proportion of mouse T cells that express IL-2 receptors after mitogen stimulation , 1986, Mechanisms of Ageing and Development.

[33]  M. Lohmann‐Matthes,et al.  Macrophage activation and induction of macrophage cytotoxicity by purified polysaccharide fractions from the plant Echinacea purpurea , 1984, Infection and immunity.

[34]  C. Biron,et al.  Increase in NK cell number and turnover rate during acute viral infection. , 1983, Journal of immunology.

[35]  S. Miller Production and renewal of murine natural killer cells in the spleen and bone marrow. , 1982, Journal of immunology.

[36]  M. Thoman,et al.  Cell-mediated immunity in aged mice: an underlying lesion in IL 2 synthesis. , 1982, Journal of immunology.

[37]  C. Henney,et al.  Display of the neutral glycolipid ganglio-n-tetraosylceramide (asialo GM1) on cells of the natural killer and T lineages. , 1982, Transplantation.

[38]  H. Yamada,et al.  Age-related changes in the function of hemopoietic stroma in mice. , 1980, Experimental hematology.

[39]  M. Kasai,et al.  A glycolipid on the surface of mouse natural killer cells , 1980, European journal of immunology.

[40]  I. Gresser,et al.  Enhancement of mouse NK cells by interferon. , 1979, Transplantation proceedings.

[41]  J. Djeu,et al.  Augmentation of mouse natural killer cell activity by interferon and interferon inducers. , 1979, Journal of immunology.

[42]  J. Roder,et al.  Target-effector interaction in the natural killer (NK) cell system. II. The isolation of NK cells and studies on the mechanism of killing. , 1978, Journal of immunology.

[43]  S. Miller,et al.  Small lymphocyte production and lymphoid cell proliferation in mouse bone marrow , 1978, Experientia.

[44]  R. Herberman,et al.  Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. I. Distribution of reactivity and specificity , 1975, International journal of cancer.

[45]  S. Miller,et al.  LYMPHOCYTE POPULATIONS IN MOUSE BONE MARROW: QUANTITATIVE KINETIC STUDIES IN YOUNG, PUBERTAL AND ADULT C3H MICE , 1975, Cell and tissue kinetics.

[46]  D. J. Voaden,et al.  Tumor inhibitors. 3. Identification and synthesis of an oncolytic hydrocarbon from American coneflower roots. , 1972, Journal of medicinal chemistry.

[47]  F. A. Anderer,et al.  Mechanism of stimulation of human natural killer cytotoxicity by arabinogalactan fromLarix occidentalis , 2005, Cancer Immunology, Immunotherapy.

[48]  K. Linde,et al.  Results of five randomized studies on the immunomodulatory activity of preparations of Echinacea. , 1995, Journal of alternative and complementary medicine.

[49]  M. Lohmann‐Matthes,et al.  Application of purified polysaccharides from cell cultures of the plant Echinacea purpurea to test subjects mediates activation of the phagocyte system. , 1991, International journal of immunopharmacology.

[50]  A. Kiderlen,et al.  Application of purified polysaccharides from cell cultures of the plant Echinacea purpurea to mice mediates protection against systemic infections with Listeria monocytogenes and Candida albicans. , 1991, International journal of immunopharmacology.

[51]  M. Sc,et al.  Relationship between large and small tumor-binding cells in the spleen and bone marrow. , 1991 .

[52]  M. Zenk,et al.  Immunologically active polysaccharides of Echinacea purpurea cell cultures , 1988 .

[53]  A. Vollmar,et al.  [Immunostimulating action of polysaccharides (heteroglycans) from higher plants]. , 1985, Arzneimittel-Forschung.

[54]  S. Miller,et al.  Quantitative changes with age in bone marrow cell populations of C3H mice. , 1974, Experimental hematology.