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Non-Functionalized Ultrasmall Silica Nanoparticles Directly and Size-Selectively Activate T Cells.
Vis, Bradley; Hewitt, Rachel E; Faria, Nuno; Bastos, Carlos; Chappell, Helen; Pele, Laetitia; Jugdaohsingh, Ravin; Kinrade, Stephen D; Powell, Jonathan J.
Afiliación
  • Vis B; Biomineral Research Group, Department of Veterinary Medicine , University of Cambridge , Madingley Road , Cambridge CB3 0ES , United Kingdom.
  • Hewitt RE; Biomineral Research Group, Department of Mineral Science and Technology , MRC Elsie Widdowson Laboratory , Fulbourn Road , Cambridge CB1 9NL , United Kingdom.
  • Faria N; Department of Chemistry , Lakehead University , Thunder Bay , Ontario P7B 5E1 , Canada.
  • Bastos C; Biomineral Research Group, Department of Veterinary Medicine , University of Cambridge , Madingley Road , Cambridge CB3 0ES , United Kingdom.
  • Chappell H; Biomineral Research Group, Department of Mineral Science and Technology , MRC Elsie Widdowson Laboratory , Fulbourn Road , Cambridge CB1 9NL , United Kingdom.
  • Pele L; Biomineral Research Group, Department of Veterinary Medicine , University of Cambridge , Madingley Road , Cambridge CB3 0ES , United Kingdom.
  • Jugdaohsingh R; Biomineral Research Group, Department of Mineral Science and Technology , MRC Elsie Widdowson Laboratory , Fulbourn Road , Cambridge CB1 9NL , United Kingdom.
  • Kinrade SD; Biomineral Research Group, Department of Veterinary Medicine , University of Cambridge , Madingley Road , Cambridge CB3 0ES , United Kingdom.
  • Powell JJ; Biomineral Research Group, Department of Mineral Science and Technology , MRC Elsie Widdowson Laboratory , Fulbourn Road , Cambridge CB1 9NL , United Kingdom.
ACS Nano ; 12(11): 10843-10854, 2018 11 27.
Article en En | MEDLINE | ID: mdl-30346692
Sub-micron-sized silica nanoparticles, even as small as 10-20 nm in diameter, are well-known for their activation of mononuclear phagocytes. In contrast, the cellular impact of those <10 nm [ i.e., ultrasmall silica nanoparticles (USSN)] is not well-established for any cell type despite anticipated human exposure. Here, we synthesized discrete populations of USSN with volume median diameters between 1.8 to 16 nm and investigated their impact on the mixed cell population of human primary peripheral mononuclear cells. USSN 1.8-7.6 nm in diameter, optimally 3.6-5.1 nm in diameter, induced dose-dependent CD4 and CD8 T-cell activation in terms of cell surface CD25 and CD69 up-regulation at concentrations above 150 µM Sitotal (∼500 nM particles). Induced activation with only ∼2.4 µM particles was (a) equivalent to that observed with typical positive control levels of Staphylococcal enterotoxin B (SEB) and (b) evident in antigen presenting cell-deplete cultures as well as in a pure T-cell line (Jurkat) culture. In the primary mixed-cell population, USSN induced IFN-γ secretion but failed to induce T-cell proliferation or the secretion of IL-2, IL-10, or IL-4. Collectively, these data indicate that USSN initiate activation, with Th1 polarization, of T cells via direct particle-cell interaction. Finally, similarly sized iron hydroxide particles did not induce the expression of T-cell activation markers, indicating some selectivity of the ultrasmall particle type. Given that humans may be exposed to ultrasmall particles and that these materials have emerging bioclinical applications, their off-target immunomodulatory effects via direct T-cell activation should be carefully considered.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T / Dióxido de Silicio / Nanopartículas Límite: Humans Idioma: En Revista: ACS Nano Año: 2018 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T / Dióxido de Silicio / Nanopartículas Límite: Humans Idioma: En Revista: ACS Nano Año: 2018 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos