| Grant number: | 14/17671-8 |
| Support Opportunities: | Regular Research Grants |
| Start date: | February 01, 2015 |
| End date: | April 30, 2017 |
| Field of knowledge: | Biological Sciences - Morphology - Cytology and Cell Biology |
| Principal Investigator: | Maria Célia Jamur |
| Grantee: | Maria Célia Jamur |
| Host Institution: | Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
| Associated researchers: | Constance Oliver |
Abstract
Mast cells are multifunctional cells of the immune system that act in both innate and acquired immunity and in various biological events such as: defense of the organism, angiogenesis and inflammatory and allergic reactions. These actions are directly related to mast cell activation which results in the liberations of diverse chemical mediators. Mast cell activation most commonly occurs through the interaction of a multivalent antigen (allergen) with immunoglobulin E (IgE) that is bound to the high affinity IgE receptor (FcµRI). Stimulation of mast cells via FcµRI activates the transcription factors NFAT and NFºB that results in cytokine production and release. The initial signal transduction events occur in lipid microdomains (lipid rafts) in the plasma membrane. Immediately after the cross-linking FcµRI, it along with other components of the signaling complex is translocated to lipid rafts. The mast cell specific gangliosides derived from GD1b are components of these lipid rafts. The cross-linking of the gangliosides by mAbAA4 results in a partial mast cell activation, similar to that seen with activation via FcµRI, but not resulting in histamine release. When the gangliosides derived from GD1b are cross-linked by mAbAA4, with time, gangliosides on the cell surface cap. The increase in the number of ganglioside caps on the cell surface correlates with the inhibition of histamine release induced via FcµRI. The objective of the present study is to characterize the role of the gangliosides derived from GD1b in the FcµRI signaling pathway. The consequence of cross-linking the gangliosides derived from GD1b on activation of NFAT and NFºB will be investigated. The role, if any, that Syk (Spleen tyrosine kinase) plays in this activation will also be studied. It will be determined if activation of the transcription factors by cross-linking the gangliosides derived from GD1b results in release of newly synthesized factors from the mast cells. Furthermore, the composition of the lipid rafts will be characterized when the gangliosides derived from GD1b are aggregated or not. The knowledge gained about the involvement of the gangliosides derived from GD1b in the signaling pathway in mast cells may reveal new therapeutic targets for treatment of allergy and inflammation. (AU)
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