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The role of mast cell specific gangliosides in modulating mediator release

Grant number: 13/12861-0
Support type:Scholarships in Brazil - Master
Effective date (Start): September 01, 2013
Effective date (End): March 31, 2015
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal researcher:Maria Célia Jamur
Grantee:Edismauro Garcia Freitas Filho
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Mast cells are immunoregulatory cells that participate in various biological events such as host defense, angiogenesis, inflammatory and allergic reactions. These events are directly related to mast cell activation and subsequent mediator release. Mast cell activation generally occurs through the interaction of a multivalent antigen (allergen) with immunoglobulin E (IgE) bound to the high-affinity receptor for immunoglobulin E (Fc[RI) on the mast cell surface. Mast cells stimulation via Fc[RI also activates transcription factors NFAT and NFºB which results in the synthesis and release of cytokines. The early events in signal transduction occur in lipid rafts in plasma membrane. Immediately after FcµRI cross-linking, FcµRI and other signaling molecules are translocated into lipid rafts. Mast cell specific gangliosides derived from GD1b are also present in lipid rafts on the surface of the plasma membrane and are associated with FcµRI in activated mast cells. The cross-linking of these gangliosides by mAb AA4 promotes a partial activation of mast cells, similar to that observed by activation via FcµRI, but does not result in histamine release. Cross-linking the gangliosides derived from GD1b results in their capping on the cell surface. With time, the caps increase on the cell surface, which correlates with the inhibition of histamine release via Fc[RI. The present study aims to characterize the role of the gangliosides derived from GD1b in the signaling pathway in mast cells. The activation of NFAT and NFºB by cross-linking the gangliosides derived from GD1b will be investigated. It will also be determined if this activation is mediated by Syk (spleen tyrosine kinase). Whether or not the activation of these transcription factors also results in the release of neo-synthesized factors by mast cells will also be evaluated. Furthermore, the composition of lipid rafts will be characterized when the gangliosides derived from GD1b are aggregated or not. The knowledge of the role of gangliosides in mast cell signaling may lead to new therapeutic targets for allergic and inflammatory processes.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FREITAS FILHO, EDISMAURO GARCIA; MARIN JACA, LUIZ AUGUSTO; BAEZA, LILIAN CRISTIANE; DE ALMEIDA SOARES, CELIA MARIA; BORGES, CLAYTON LUIZ; OLIVER, CONSTANCE; JAMUR, MARIA CELIA. Proteomic Analysis of Lipid Rafts from RBL-2H3 Mast Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 16 AUG 2 2019. Web of Science Citations: 0.
MARCELINO DA SILVA, ELAINE ZAYAS; FREITAS-FILHO, EDISMAURO GARCIA; DE SOUZA-JUNIOR, DEVANDIR ANTONIO; PINTO DASILVA, LUIS LAMBERTI; JAMUR, MARIA CELIA; OLIVER, CONSTANCE. Adaptor protein-3: A key player in RBL-2H3 mast cell mediator release. PLoS One, v. 12, n. 3 MAR 8 2017. Web of Science Citations: 2.
FREITAS FILHO, EDISMAURO GARCIA; MARCELINO DA SILVA, ELAINE ZAYAS; ZANOTTO, CAMILA ZILIOTTO; OLIVER, CONSTANCE; JAMUR, ANDMARIA CELIA. Cross-Linking Mast Cell Specific Gangliosides Stimulates the Release of Newly Formed Lipid Mediators and Newly Synthesized Cytokines. Mediators of Inflammation, 2016. Web of Science Citations: 3.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.