title: Cross-Linking Mast Cell Specific Gangliosides Stimulates the Release of Newly Formed Lipid Mediators and Newly Synthesized Cytokines.
abstract: Mast cells are immunoregulatory cells that participate in inflammatory processes. Cross-linking mast cell specific GD1b derived gangliosides by mAbAA4 results in partial activation of mast cells without the release of preformed mediators. The present study examines the release of newly formed and newly synthesized mediators following ganglioside cross-linking. Cross-linking the gangliosides with mAbAA4 released the newly formed lipid mediators, prostaglandins D2 and E2, without release of leukotrienes B4 and C4. The effect of cross-linking these gangliosides on the activation of enzymes in the arachidonate cascade was then investigated. Ganglioside cross-linking resulted in phosphorylation of cytosolic phospholipase A2 and increased expression of cyclooxygenase-2. Translocation of 5-lipoxygenase from the cytosol to the nucleus was not induced by ganglioside cross-linking. Cross-linking of GD1b derived gangliosides also resulted in the release of the newly synthesized mediators, interleukin-4, interleukin-6, and TNF-α. The effect of cross-linking the gangliosides on the MAP kinase pathway was then investigated. Cross-linking the gangliosides induced the phosphorylation of ERK1/2, JNK1/2, and p38 as well as activating both NFκB and NFAT in a Syk-dependent manner. Therefore, cross-linking the mast cell specific GD1b derived gangliosides results in the activation of signaling pathways that culminate with the release of newly formed and newly synthesized mediators.
authors: Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: Edismauro Garcia Freitas
authors: 0000-0002-1910-1085
authors: EG
authors: Filho
authors: Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: Elaine Zayas Marcelino
authors: 0000-0002-2749-6275
authors: EZ
authors: da Silva
authors: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: Camila Ziliotto
authors: CZ
authors: Zanotto
authors: Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: Constance
authors: 0000-0002-8633-4612
authors: C
authors: Oliver
authors: Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: Maria Célia
authors: 0000-0001-7065-8543
authors: MC
authors: Jamur
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D005732:Gangliosides / Q000378:metabolism*; D054513:Group IV Phospholipases A2 / Q000378:metabolism; D015151:Immunoblotting; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010766:Phosphorylation; D011457:Prostaglandins D / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D005732:Gangliosides; D015850:Interleukin-6; D015289:Leukotrienes; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D011457:Prostaglandins D; D011458:Prostaglandins E; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D048056:Mitogen-Activated Protein Kinase 9; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases; D054513:Group IV Phospholipases A2