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Fullerene Nanomaterials Inhibit the Allergic Response¹

John J. Ryan^*, Henry R. Bateman, Alex Stover, Greg Gomez, Sarah K. Norton^*, Wei Zhao, Lawrence B. Schwartz, Robert Lenk and Christopher L. Kepley^2,

^* Department of Biology, [s] Department of Pediatrics, and [s] Department of Internal Medicine, Virginia Commonwealth University Health Systems, Richmond, VA 23294; and Luna Innovations, Danville, VA 24541

Fullerenes are a class of novel carbon allotropes that may have practical applications in biotechnology and medicine. Human mast cells (MC) and peripheral blood basophils are critical cells involved in the initiation and propagation of several inflammatory conditions, mainly type I hypersensitivity. We report an unanticipated role of fullerenes as a negative regulator of allergic mediator release that suppresses Ag-driven type I hypersensitivity. Human MC and peripheral blood basophils exhibited a significant inhibition of IgE dependent mediator release when preincubated with C₆₀ fullerenes. Protein microarray demonstrated that inhibition of mediator release involves profound reductions in the activation of signaling molecules involved in mediator release and oxidative stress. Follow-up studies demonstrated that the tyrosine phosphorylation of Syk was dramatically inhibited in Ag-challenged cells first incubated with fullerenes. In addition, fullerene preincubation significantly inhibited IgE-induced elevation in cytoplasmic reactive oxygen species levels. Furthermore, fullerenes prevented the in vivo release of histamine and drop in core body temperature in vivo using a MC-dependent model of anaphylaxis. These findings identify a new biological function for fullerenes and may represent a novel way to control MC-dependent diseases including asthma, inflammatory arthritis, heart disease, and multiple sclerosis.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by National Institutes of Health Grants R01-AI27517 (to L.B.S.) and K08-AI057357 (to W.Z.) and by the Food Allergy and Anaphylaxis Network (to C.L.K.).

² Address correspondence and reprint requests to Dr. Chris Kepley, PhD, MBA Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, P.O. Box 980263 MCV Station, Richmond, VA 23298. E-mail address: clkepley{at}vcu.edu

³ Abbreviations used in this paper: MC, mast cell; PBB, peripheral blood basophils; ROS, reactive oxygen species; DCF, dichlorofluorescein.