title: Fullerene nanomaterials inhibit the allergic response.
abstract: 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 C(60) 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.
authors.affiliation: Department of Biology, Virginia Commonwealth University Health Systems, Richmond, VA 23294, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Ryan
authors.forename: Henry R
authors.initials: HR
authors.lastname: Bateman
authors.forename: Alex
authors.initials: A
authors.lastname: Stover
authors.forename: Greg
authors.initials: G
authors.lastname: Gomez
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Norton
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Schwartz
authors.forename: Robert
authors.initials: R
authors.lastname: Lenk
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Kepley
mesh_terms: D000707:Anaphylaxis / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D001491:Basophils / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D037741:Fullerenes / Q000494:pharmacology* / Q000627:therapeutic use; D006636:Histamine Release / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000008:administration & dosage / Q000096:biosynthesis / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000627:therapeutic use*; D011485:Protein Binding / Q000276:immunology; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D037741:Fullerenes; D007166:Immunosuppressive Agents; D007073:Immunoglobulin E; C069837:fullerene C60