asialo-gm1-ganglioside and Body-Weight

A number of methods have been developed to assess the impact of a xenobiotic on the various components of the immune system. For risk analysis, it is necessary to determine what degree of chemically induced immune perturbation translates into altered host resistance. Natural killer (NK) cells play a pivotal role in the innate immune system with the ability to lyse cells infected with intracellular pathogens and certain tumors without previous exposure to the antigen. Spontaneous NK activity in B6C3F1 mice could be incrementally and consistently decreased by 20 to > or =80% by the intravenous administration of a range of dilutions of anti-asialo GM1 (AAGM1) antibody. The decrease in spontaneous NK activity following a single iv administration of AAGM1 antibody persisted for up to approximately 3 weeks when the initial suppression (e.g., 24 h after AAGM1 antibody injection) was almost 100%. Treatment with AAGM1, however, did not appear to perturb the function of other immune cells, based on results of the plaque assay, the mixed lymphocyte response, the cytotoxic T lymphocyte assay, the reticuloendothelial system clearance of sRBC assay, and the Streptococcus pneumoniae host resistance assay. Following a > or =80% decrease in spontaneous NK activity in mice, challenge with > or =1 x 10(3) B16F10 melanoma cells resulted in an increase in tumor burden based on the number of lung nodules. However, following challenge with 1 x 10(5) melanoma cells, a significant increase in tumor burden in mice was not observed until spontaneous NK activity had been decreased by > or =50-60%. Altered host resistance is a function not only of the magnitude of the decrease in NK activity but also of the magnitude of the challenge to the host.

Topics: Animals; Antibodies; Body Weight; Cell Count; Cells, Cultured; Crosses, Genetic; Cytotoxicity Tests, Immunologic; Dose-Response Relationship, Immunologic; Erythrocytes; G(M1) Ganglioside; Immunocompromised Host; Immunosuppression Therapy; Immunosuppressive Agents; Killer Cells, Natural; Melanoma; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Neoplasm Transplantation; Organ Size; Spleen; Streptococcus pneumoniae; T-Lymphocytes; Xenograft Model Antitumor Assays

Administration of dextran sulfate to mice, given in the drinking water results in acute or subacute colonic inflammation, depending on the administration protocol. This colonic inflammation exhibits ulceration, healing and repair, and a therapeutic response that makes it valuable for the study of mechanisms that could act in the pathogenesis of human ulcerative colitis, a disease thought to have an immunologically dependent pathogenesis. To investigate if immunological mechanisms were involved in the induction of colonic inflammation in this model, mice with different degrees of immunodeficiency were used. It was shown that dextran sulfate induced colitis could be induced in Balb/c mice depleted of CD4(+) helper T cells by treatment with monoclonal antibodies preceded by adult thymectomy. The depletion of CD4(+) was verified by flow cytometric analysis. Furthermore, the colonic inflammation could equally be induced in athymic CD-1 nu/nu mice lacking thymus-derived T cells, in T and B-cell deficient SCID mice, and also in SCID mice depleted of NK cells by treatment with anti-asialo GM1 antibodies. The NK-cell depletion was verified by measuring spleen NK-cell activity. The resulting colonic inflammation in all these types of deficient mice was qualitatively comparable, as shown by clinical and histological appearance. These results indicate that the presence of functional T, B and NK cells is not crucial for the induction of dextran sulfate colitis in mice.

Topics: Administration, Oral; Analysis of Variance; Animals; Antibodies, Monoclonal; Antiviral Agents; B-Lymphocytes; Body Weight; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Female; Flow Cytometry; Fluorescent Antibody Technique, Direct; G(M1) Ganglioside; Immunoglobulin G; Killer Cells, Natural; Lymphoid Tissue; Mice; Mice, Inbred BALB C; Mice, Nude; Mice, SCID; Organ Size; Specific Pathogen-Free Organisms; T-Lymphocytes, Helper-Inducer; Thymectomy

The influence of the degree of saturation and the concentration of dietary fat on murine natural killer (NK) cell activity was investigated using C3H/HeN and C57BL/6N mice. Mice were fed purified diets containing either 0% fat (fat free), 5 or 20% safflower oil or 5 or 20% palm oil. Safflower oil and palm oil were used because they are comparable in carbon chain length but vary in the amount of linoleic acid [18:2(n-6)]. Cytotoxicity of splenic NK cells from mice stimulated or unstimulated by the interferon inducer poly I:C was measured against either the YAC-1 lymphoma or line 168 mammary tumor targets. The number of asialo GM1+ cells was not influenced by concentration or degree of saturation of dietary fat. Generally, dietary fat had no consistent influence on NK cell cytotoxicity of spleen cells from either the high responder C3H/HeN mice or the moderate responder C57BL/6N mice against either tumor target. The level of 18:2(n-6) in NK cell-enriched splenic lymphocytes increased with greater levels of dietary safflower oil. Nevertheless, there appeared to be no correlation between lymphocyte fatty acid composition and NK cell cytotoxic capabilities. Therefore, the concentration of dietary safflower or palm oil, and thus 18:2 (n-6), did not appear to effect the number or activity of murine NK cells.

Topics: Animals; Body Weight; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Dietary Fats; Female; G(M1) Ganglioside; Glycosphingolipids; Immunity, Cellular; Killer Cells, Natural; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Species Specificity; Spleen