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2010 ; 3
(4
): 158-69
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English Wikipedia
A new class of human mast cell and peripheral blood basophil stabilizers that
differentially control allergic mediator release
#MMPMID20718816
Norton SK
; Dellinger A
; Zhou Z
; Lenk R
; Macfarland D
; Vonakis B
; Conrad D
; Kepley CL
Clin Transl Sci
2010[Aug]; 3
(4
): 158-69
PMID20718816
show ga
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 C(70)-tetraglycolic acid
significantly inhibited degranulation and cytokine production from mast cells and
basophils, while C(70)-tetrainositol blocked only cytokine production in mast
cells and degranulation and cytokine production in basophils. The early phase of
FcepsilonRI 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. C(70)-tetraglycolic acid
was able to block mast cell-driven anaphylaxis in vivo, while C(70)-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
FcepsilonRI-specific molecules in mast cells and basophils. These next generation
fullerene derivatives represent a new class of compounds that interfere with
FcepsilonRI signaling pathways to stabilize mast cells and basophils. Thus,
fullerene-based therapies may be a new approach for treating allergic diseases.