asialo-gm1-ganglioside and Chronic-Disease

Cancer progression involves carcinogenesis, an increase in tumour size, and metastasis. Here, we investigated the effect of overexpressed CXC chemokine ligand 14 (CXCL14) on these processes by using CXCL14/BRAK (CXCL14) transgenic (Tg) mice. The rate of AOM/DSS-induced colorectal carcinogenesis in these mice was significantly lower compared with that for isogenic wild type C57BL/6 (Wt) mice. When tumour cells were injected into these mice, the size of the tumours that developed and the number of metastatic nodules in the lungs of the animals were always significantly lower in the Tg mice than in the Wt ones. Injection of anti-asialo-GM1 antibodies to the mice before and after injection of tumour cells attenuated the suppressing effects of CXCL14 on the tumor growth and metastasis, suggesting that NK cell activity played an important role during CXCL14-mediated suppression of tumour growth and metastasis. The importance of NK cells on the metastasis was also supported when CXCL14 was expressed in B16 melanoma cells. Further, the survival rates after tumour cell injection were significantly increased for the Tg mice. As these Tg mice showed no obvious abnormality, we propose that CXCL14 to be a promising molecular target for cancer suppression/prevention.

Topics: Animals; Antigens, Ly; Autoantibodies; Cell Transformation, Neoplastic; Chemokines, CXC; Chronic Disease; Colitis; Disease Models, Animal; Female; G(M1) Ganglioside; Galactosylceramides; Killer Cells, Natural; Lung Neoplasms; Lymphocyte Depletion; Melanoma, Experimental; Mice; Mice, Transgenic; Neoplasms; NK Cell Lectin-Like Receptor Subfamily B; Tumor Burden

Toxoplasmosis is a potentially fatal opportunistic infection of immunocompromised hosts. Improved animal models of toxoplasmosis are needed to more nearly approximate conditions that occur in immunocompromised humans. The development of models of toxoplasmosis using human peripheral blood lymphocytes (hu-PBL) transplanted into severe combined immunodeficiency (SCID) mice is described here. Transplantation of hu-PBL into SCID mice without prior conditioning of the mice resulted in detectable differences in quantitative histological scores of brain inflammation due to Toxoplasma gondii infection, but did not alter mortality when compared to SCID mouse controls. The lack of detectable differences in survival were due to inadequate engraftment of hu-PBL, as assessed by flow cytometry. Unconditioned hu-PBL SCID mice had low titre T. gondii-specific antibody detectable after infection. When pretransplantation conditioning with irradiation and antiasialo GM 1 (n-glucolyl neuraminic acid) antibody was used, prolonged hu-PBL engraftment was observed in SCID mice, which was associated with worsened histopathology and usually impaired survival when compared with SCID mouse controls. When pretransplantation conditioning with irradiation, antiasialo GM antibody and polyethylene glycol-conjugated IL-2 was used, prolonged hu-PBL engraftment was also documented, but this did not affect survival from T. gondii infection when compared with similarly conditioned SCID mouse controls. The latter conditioning protocol resulted in hu-PBL SCID mice producing high titre T. gondii-specific antibody after infection. Conditioned hu-PBL SCID mice had evidence of increased T. gondii-induced inflammatory scores when compared with conditioned SCID mice. These models show promise for the study of the pathogenesis of toxoplasmosis and conditioned hu-PBL SCID mice may have applications for the evaluation of novel therapies for toxoplasmosis in immunocompromised humans.

Topics: Acute Disease; Animals; Antibodies; Antibodies, Protozoan; Chronic Disease; Cytotoxicity Tests, Immunologic; Disease Models, Animal; Flow Cytometry; G(M1) Ganglioside; Humans; Killer Cells, Natural; Liver; Lymphocyte Count; Lymphocyte Transfusion; Mice; Mice, SCID; Spleen; Survival Rate; Toxoplasma; Toxoplasmosis, Animal; Transplantation Conditioning; Whole-Body Irradiation

Serum IgG in a patient with chronic polyneuropathy after Mycoplasma pneumoniae infection reacted with ganglioside GM1, GD1b and asialo-GM1 on thin-layer chromatograms using an immunostaining technique as well as an enzyme-linked immunosorbent assay, suggesting that the galactosyl (beta 1-3)N-acetylgalactosaminyl moiety could be a target antigen in this patient. Serum IgG reacting with these glycolipids may be involved in the pathogenesis of both motor and sensory neuropathies in this patient.

Topics: Adolescent; Adult; Aged; Autoantibodies; Autoimmune Diseases; Child; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Gangliosides; Humans; Immunoglobulin G; Male; Middle Aged; Neurologic Examination; Pneumonia, Mycoplasma; Polyradiculoneuropathy

Topics: Acute Disease; Alopecia; Animals; Chronic Disease; Dermatitis; Female; G(M1) Ganglioside; Glycosphingolipids; Graft vs Host Disease; Mice; Mice, Inbred C57BL; Mice, Inbred DBA

The effect of recombinant human interleukin-2 (rIL-2) on the course of experimental chronic respiratory tract infection caused by Klebsiella pneumoniae in mice was examined. rIL-2 was administered subcutaneously once a day for 7 or 14 days, starting 2 weeks after the mice were infected. Administration of 2 or 20 micrograms of rIL-2 per mouse daily for 7 days reduced bacterial counts in the lungs dose dependently. At a dose of 0.2 microgram per day, proliferation of bacteria in the lungs was suppressed after 14 days of administration. Agglutinin titers in serum were not affected by rIL-2 treatment. Monocyte and lymphocyte counts in peripheral blood were increased by administration of 20 micrograms of rIL-2 daily for 14 days but not by treatment for 7 days. In addition, clearance of bacteria from the lungs after aerosol exposure was enhanced by treatment for 7 days before infection. Thus, rIL-2 acted therapeutically or prophylactically in the presence or absence, respectively, of a specific antigen. These effects were not abolished by anti-asialo GM1 antibody. This suggests that activation of natural killer cells does not play a critical role in the therapeutic and prophylactic effects of rIL-2.

Topics: Aerosols; Agglutination Tests; Animals; Antibodies; Chronic Disease; Female; G(M1) Ganglioside; Glycosphingolipids; Interleukin-2; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Leukocyte Count; Lung Diseases; Mice; Mice, Inbred CBA; Recombinant Proteins; Respiratory Tract Infections