A New Class of Human Mast Cell and Peripheral Blood Basophil Stabilizers that Differentially Control Allergic Mediator Release

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Christopher Kepley, Associate Professor (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: Treatments for allergic disease block the effects of mediators released from activated mast cells and blood basophils. A panel of fullerene derivatives was synthesized and tested for their ability to preempt the release of allergic mediators in vitro and in vivo. The fullerene C70 -tetraglycolic acid significantly inhibited degranulation and cytokine production from mast cells and basophils, while C70 –tetrainositol blocked only cytokine production in mast cells and degranulation and cytokine production in basophils. The early phase of FceRI inhibition was dependent on the blunted release of intracellular calcium stores, elevations in reactive oxygen species, and several signaling molecules. Gene microarray studies further showed the two fullerene derivatives inhibited late phase responses in very different ways. C70 -tetraglycolic acid was able to block mast cell-driven anaphylaxis in vivo, while C70 -tetrainositol did not. No toxicity was observed with either compound. These findings demonstrate the biological effects of fullerenes critically depends on the moieties added to the carbon cage and suggest they act on different FceRI-specific molecules in mast cells and basophils. These next generation fullerene derivatives represent a new class of compounds that interfere with FceRI signaling pathways to stabilize mast cells and basophils. Thus, fullerene based therapies may be a new approach for treating allergic diseases.

Additional Information

Clinical and Translational Science, 3(4),158-69
Language: English
Date: 2010
drug action, drug design, inflammation, mast cell, basophil, nanomedicine

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