Cross-linking Mast Cell Specific Gangliosides Stimulates the Release of Newly Formed Lipid Mediators and Newly Synthesized Cytokines: An Advanced Study

Mast cells are immune-regulatory cells that play a role in the inflammatory response. Mast cells are partially activated without the release of preformed mediators when GD1b generated gangliosides are cross-linked by mAbAA4. Following ganglioside cross-linking, the release of newly formed and newly synthesised mediators is investigated. The newly synthesised lipid mediators, prostaglandins D2 and E2, were produced when the gangliosides were crosslinked with mAbAA4, however leukotrienes B4 and C4 were not released. The impact of cross-linking these gangliosides on the activation of arachidonate cascade enzymes was then examined. The phosphorylation of cytosolic phospholipase A2 and enhanced production of cyclooxygenase-2 were both caused by ganglioside cross-linking. Ganglioside cross-linking did not cause 5-lypoxygenase to translocate from the cytosol to the nucleus. The newly produced mediators interleukin-4, interleukin-6, and TNF- were also released after cross-linking of GD1b generated gangliosides. After that, the impact of cross-linking the gangliosides on the MAP kinase pathway was examined. The phosphorylation of ERK1/2, JNK1/2, and p38, as well as the activation of both NFB and NFAT, was activated by cross-linking the gangliosides in a Syk-dependent way. As a result of cross-linking the mast cell-specific GD1b derived gangliosides, signalling pathways are activated, culminating in the release of newly generated and synthesised mediators. The current study contributes to a better understanding of the wide range of potential methods by which mast cells repress, enhance, and modulate non-FcRI driven immune responses.

Author (s) Details

Edismauro Garcia Freitas Filho
Department of Cell and Molecular Biology and Pathogenic Bioagents, Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.

Elaine Zayas Marcelino da Silva
Department of Cell and Molecular Biology and Pathogenic Bioagents, Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.

Camila Ziliotto Zanotto
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.

Constance Oliver
Department of Cell and Molecular Biology and Pathogenic Bioagents, Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.

Maria Célia Jamur
Department of Cell and Molecular Biology and Pathogenic Bioagents, Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil.

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