g(m1)-ganglioside and Colitis

Guillain-Barré syndrome (GBS) is the most common cause of acute neuromuscular paralysis. Sera from patients with GBS following Campylobacter jejuni infection frequently have autoantibody to GM 1 ganglioside in the acute phase of the illness. We revealed that the lipopolysaccharide (LPS) of C. jejuni that was isolated from a GBS patient has the oligosaccharide structure [Gal beta 1-3 GalNAc beta 1-4 (NeuAc alpha 2-3) Gal beta 1-], which is identical to the terminal tetrasaccharide of GM 1 ganglioside. (1) Infection by C. jejuni that bears the GM 1-like lipopolysaccharide associated with the serotypic determinant of PEN 19 induces high production of IgG 1 and IgG 3 anti-GM 1 antibodies with help of T cells. (2) IgG anti-GM 1 antibody binds to motor nerve terminal axons, inhibits motoneuron excitability, and produces the development of GBS.

Topics: Animals; Autoantibodies; Campylobacter Infections; Campylobacter jejuni; Colitis; G(M1) Ganglioside; Humans; Immunoglobulin G; Lipopolysaccharides; Polyradiculoneuropathy; T-Lymphocytes

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

Initially the intraepithelial leukocytes (IEL) of specific pathogen free (SPF) mice were compared with those of mice held without isolation and were found to differ markedly in total number and distribution of cell surface antigens. The IEL from SPF mice expressed significantly less Thy-1, Lyt-1, and Lyt-2 antigens than their conventional counterparts. The local cell-mediated immune response of mucosal lymphocytes to an enteric murine coronavirus (MHV-Y) was studied in inbred strains of naive SPF mice. A potent in vitro cytotoxic activity was demonstrated by mucosal leukocytes, especially IEL, and spleen cells for MHV-Y-infected syngeneic and allogeneic target cells. The cytotoxicity was not restricted by the major histocompatibility complex. Targets infected with Pichinde virus, an enveloped nonenterotropic virus, were not lysed by these cells. The phenotype of the IEL effector cell was asialo GM1+, Thy-1-, Lyt-1-, Lyt-2-. This cell represents a small subpopulation of the total IEL. After the in vivo administration of anti-asialo GM1 sera, the virus-specific cytotoxic function of the IEL was markedly diminished in in vitro assays, and there was enhanced persistence of virus in gut tissues in vivo. The IEL effector population is defined as a natural killer-like cell that appears to be active in the defense of the gut epithelium to a murine enteric coronavirus.

Topics: Animals; Antigens, Surface; Cell Separation; Centrifugation, Density Gradient; Colitis; Coronaviridae Infections; Cytotoxicity, Immunologic; Epithelium; Female; G(M1) Ganglioside; Glycosphingolipids; Immune Sera; Intestinal Mucosa; Killer Cells, Natural; Mice; Mice, Inbred A; Mice, Inbred CBA; Mice, Inbred DBA; Phenotype