Inhibition of lipopolysaccharide‐induced monocyte interleukin 1 secretion by gangliosides

Cavaillon, Jean‐Marc; Fitting, Catherine

doi:10.1002/eji.1830160823

Cited by 22 publications

(3 citation statements)

References 28 publications

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“…A. Werkmeister, unpublished observations), an event which is unaffected by Arg-Gly-Asp-containing peptides (20). Gangliosides have also been implicated in a number of cell types in such diverse receptor-mediated processes as the binding of various growth factors (4,23) and the binding of lipopolysaccharide (8), various bacterial toxins (15,43), viruses (26), thyroid stimulating hormone (1), transferrin (28), and interferon (3). With the identification of specific glycoprotein receptors for many of these factors, it is now becoming apparent that the role of gangliosides is that of an accessory molecule to facilitate binding or to modulate receptor function rather than functioning themselves as specific receptors.…”

Section: Discussionmentioning

confidence: 96%

Synergism between membrane gangliosides and Arg-Gly-Asp-directed glycoprotein receptors in attachment to matrix proteins by melanoma cells.

Burns

Lucas

Krissansen

et al. 1988

The Journal of Cell Biology

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Abstract. The identification of specific cell surface glycoprotein receptors for Arg-Gly-Asp-containing extracellular matrix proteins such as fibronectin has focused attention on the role of gangliosides in this process. Is their involvement dependent or independent of the protein receptors? In attachment assays with cells from a human melanoma cell line, titration experiments with an antibody (Mel 3) with specificity for the disialogangliosides GD2 and GD3, used together with a synthetic peptide containing the cell binding sequence Arg-Gly-Asp, show that their joint effect is synergistic. Both the Mel 3 antibody and the synthetic peptide individually cause rapid detachment of melanoma cells from fibronectin substrate but, when used together, much smaller concentations of both are required to achieve the same effect. The Mel 3 antibody was not nonspecifically reducing receptor binding to the Arg-Gly-Asp sequence since, in binding assays with radiolabeled peptide performed with cells in suspension, very little peptide is bound by the melanoma cells under these conditions but addition of Mel 3, an antibody of IgM isotype, causes a two-to threefold increase in specific binding. The simplest interpretation of these data is that the Mel 3 antibody is causing sufficient clustering of membrane gangliosides in local areas and producing a favorably charged environment to facilitate peptide binding by specific glycoprotein receptors.understanding of cell attachment to extracellular matrix proteins will provide insights into such processes as cell migration and spreading, and tissue invasion by tumor cells. For this reason, the mechanisms by which different cells attach to fibronectin have been much studied and it is now clear that more than one interaction is involved. Gangliosides have been suggested as candidate receptors for fibronectin since their addition to cultures caused rounding up and detachment of cells from the fibronectin substrate (24,29,47). Also, the insertion of gangliosides into the membranes of ganglioside-deficient cells enabled them to bind fibronectin on the cell surface (40), and mAbs directed against determinants on the carbohydrates of the gangliosides GD2 and GD3 (41) prevented the attachment of melanoma cells to extracellular matrix proteins including fibronectin (12,45).In another approach, Pierschbacher and colleagues identified a peptide within the cell-binding domain of fibronectin that mediated the cell attachment activity of this molecule (31-33), and Hayman et al. (18) and Yamada and Kennedy (46) went on to demonstrate that peptides containing the sequence arginyl-glycyl-aspartic acid (Arg-Gly-Asp) caused detachment of cultured cells from their substratum and prevented baby hamster kidney and Chinese hamster ovary cells from spreading on fibronectin substrates. From this information, Pytela et al. (35) were able to identify a specific glycoprotein receptor of ~140 kD on osteosarcoma cells and rat fibroblasts. It is now apparent that the fibronectin receptor thus isolated is but one of a ...

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Section: Discussionmentioning

confidence: 96%

Synergism between membrane gangliosides and Arg-Gly-Asp-directed glycoprotein receptors in attachment to matrix proteins by melanoma cells.

Burns

Lucas

Krissansen

et al. 1988

The Journal of Cell Biology

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“…In our hands, however, the ganglioside-mediated inhibition cannot be overcome by high amounts (10¥) of either IL-4 or GM-CSF (data not shown). The modulation of signal transduction by gangliosides might result in the suppression of Nf-k-B and changes in the cytokine network, as described for T cells [20] and monocytes [36,37]. Furthermore, there is evidence that gangliosides alter many different signalling pathways initiated by receptor-associated tyrosine kinases or mediated by protein kinase C, MAP kinases and other kinases [11].…”

Section: Discussionmentioning

confidence: 98%

Gangliosides inhibit the development from monocytes to dendritic cells

Wölfl

Batten

Posovszky

et al. 2002

Clinical and Experimental Immunology

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SUMMARYDendritic cell (DC) development and function is critical in the initiation phase of any antigen-specific immune response against tumours. Impaired function of DC is one explanation as to how tumours escape immunosurveillance. In the presence of various soluble tumour-related factors DC precursors lose their ability to differentiate into mature DC and to activate T cells. Gangliosides are glycosphingolipids shed by tumours of neuroectodermal origin such as melanoma and neuroblastoma. In this investigation we address the question of whether gangliosides suppress the development and function of monocyte-derived DC in vitro . In the presence of gangliosides, the monocytic DC precursors showed increased adherence, cell spreading and a reduced number of dendrites. The expression of MHC class II molecules, co-stimulatory molecules and the GM-CSF receptor (CD116) on the ganglioside-treated DC was significantly reduced. Furthermore, the function of ganglioside-treated DC was impaired as observed in endocytosis, chemotactic and T cell proliferation assays. In contrast to monocytic DC precursors, mature DC were unaffected even when higher doses of gangliosides were added to the culture. With regard to their carbohydrate structure, five different gangliosides (GM2, GM3, GD2, GD3, GT1b), which are typically shed by melanoma and neuroblastoma, were tested for their ability to suppress DC development and function. Suppression was induced by GM2, but not by the other gangliosides. These data suggest that certain gangliosides impair DC precursors, implying a possible mechanism for tumour escape.

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“…These findings, combined with the fact that gangliosides are also known to suppress the production of ‘danger signals’ (i.e. inflammatory cytokines such as TNF‐α and IL‐1β) by monocytes, 34,35 and directly induce production of anti‐inflammatory cytokines (i.e. IL‐10) by T lymphocytes, 36 allow us to speculate that ovarian tumour‐derived gangliosides may be important mediators of the release of immunosuppressive cytokines in the ascitic fluid and plasma of ovarian cancer patients, a condition critical for the creation of a highly immunosuppressive microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Increased levels of gangliosides in the plasma and ascitic fluid of patients with advanced ovarian cancer

Santin

Ravindranath

Bellone

et al. 2004

BJOG

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Objectives To assess the expression of total gangliosides in primary ovarian cancer cell lines, ascitic fluid and plasma of advanced ovarian cancer patients. Design A prospective study. Setting The Department of Obstetrics and Gynecology at the University of Arkansas for Medical Sciences and the Laboratory of Glycolipid Immunotherapy, John Wayne Cancer Institute. Population Twenty‐two women diagnosed with advanced ovarian cancer and seven normal female controls. Methods Total gangliosides shedding from primary ovarian cancer cell lines were measured by estimating lipid‐associated sialic acids (LASAs test) and compared with the ganglioside levels shed by primary cervical and uterine cancer cell lines. In addition, plasma and ascitic samples from advanced ovarian cancer patients were collected at the time of surgery and analysed for the presence of total gangliosides. Main outcome measures Levels of total ganglioside in plasma and ascites fluid samples drawn from ovarian cancer patients, relative to total gangliosides levels in plasma from normal female controls. Results All primary ovarian tumours secreted high levels of total gangliosides (mean 4 mg/mL, range between 2.7 and 4.8 mg/mL/105 cells/24 h) when compared with primary cervical cancers (mean 1.4 mg/mL, range between 0.7 and 2.2 mg/mL/105 cells/24 h) (P < 0.008) and uterine carcinoma cell lines (mean 1.4 mg/mL, range between 1.3 and 1.6 mg/mL/105 cells/24 h) (P < .004). Elevated levels of total gangliosides were detected in the plasma [mean (SD) 31 (12) mg/mL, range between 18 and 57 mg/mL] (P < .001), and in the peritoneal fluid [mean (SD) 27 (9) mg/mL, range between 14 and 40 mg/mL] (P < .003) of ovarian cancer patients when compared with the levels detectable in the plasma samples of normal female controls tested [mean (SD) 15 (2) mg/mL, range between 12 and 18 mg/mL]. Conclusions Increased serum levels of total gangliosides may reflect shedding or release of gangliosides from the surface of ovarian tumour cells. Secretion of gangliosides may play an important role in the inhibition of anti‐tumour immune function commonly observed in advanced ovarian cancer.

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Inhibition of lipopolysaccharide‐induced monocyte interleukin 1 secretion by gangliosides

Cited by 22 publications

References 28 publications

Synergism between membrane gangliosides and Arg-Gly-Asp-directed glycoprotein receptors in attachment to matrix proteins by melanoma cells.

Synergism between membrane gangliosides and Arg-Gly-Asp-directed glycoprotein receptors in attachment to matrix proteins by melanoma cells.

Gangliosides inhibit the development from monocytes to dendritic cells

Increased levels of gangliosides in the plasma and ascitic fluid of patients with advanced ovarian cancer

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