title: Single-walled carbon nanotube exposure induces membrane rearrangement and suppression of receptor-mediated signalling pathways in model mast cells.
abstract: Carbon nanotubes (CNT) are environmental challenges to the respiratory and gastrointestinal mucosa, and to the dermal immune system. Mast cells (MC) are pro-inflammatory immunocytes that reside at these interfaces with the environment. Mast cells are sources of pro-inflammatory mediators (histamine, serotonin, matrix-active proteases, eicosanoids, prostanoids, cytokines and chemokines), which are released in a calcium-dependent manner following immunological challenge or physico-chemical stimulation. Since C-60 fullerenes, which share geometry with CNT, are suppressive of mast cell-driven inflammatory responses, we explored the effects of unmodified SWCNT aggregates on mast cell signaling pathways, phenotype and pro-inflammatory function. We noted SWCNT suppression of antigen-induced signalling pathways and pro-inflammatory degranulation responses. Mast cells recognize unmodified SWCNT by remodeling the plasma membrane, disaggregating the cortical actin cytoskeleton and relocalizing clathrin. Clathrin was also identified as a component of an affinity-purified 'interactome' isolated from MC using an SWCNT affinity matrix for mast cell lysates. Together, these data are consistent with the ability of SWCNT to suppress mast cell pro-inflammatory function via a novel recognition mechanism.
authors.affiliation: Laboratory of Immunology and Signal Transduction, Division of Natural Sciences and Mathematics, Chaminade University, Honolulu, HI, United States.
authors.forename: Eric Y
authors.initials: EY
authors.lastname: Umemoto
authors.affiliation: Laboratory of Immunology and Signal Transduction, Division of Natural Sciences and Mathematics, Chaminade University, Honolulu, HI, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Speck
authors.affiliation: Laboratory of Immunology and Signal Transduction, Division of Natural Sciences and Mathematics, Chaminade University, Honolulu, HI, United States.
authors.forename: Lori M N
authors.initials: LM
authors.lastname: Shimoda
authors.affiliation: Laboratory of Immunology and Signal Transduction, Division of Natural Sciences and Mathematics, Chaminade University, Honolulu, HI, United States; Undergraduate Program in Computer Sciences, Division of Natural Sciences and Mathematics, Chaminade University, Honolulu, HI, United States.
authors.forename: Kara
authors.initials: K
authors.lastname: Kahue
authors.affiliation: Laboratory of Immunology and Signal Transduction, Division of Natural Sciences and Mathematics, Chaminade University, Honolulu, HI, United States.
authors.forename: Carl
authors.initials: C
authors.lastname: Sung
authors.affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, United States.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Stokes
authors.affiliation: Laboratory of Immunology and Signal Transduction, Division of Natural Sciences and Mathematics, Chaminade University, Honolulu, HI, United States; Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, United States. Electronic address: hturner@chaminade.edu.
authors.forename: Helen
authors.initials: H
authors.lastname: Turner
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects* / Q000648:ultrastructure; D002966:Clathrin / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects; D037741:Fullerenes / Q000633:toxicity; D054819:Hexosaminidase B / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008407:Mast Cells / Q000187:drug effects* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D037742:Nanotubes, Carbon / Q000633:toxicity*; D017455:Receptors, IgE / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D002966:Clathrin; D037741:Fullerenes; D037742:Nanotubes, Carbon; D017455:Receptors, IgE; D054819:Hexosaminidase B; D002118:Calcium
keywords: Carbon nanotubes; Fullerenes; Inflammation; Mast cells