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Interactions of silica nanoparticles with lung epithelial cells and the association to flotillins

  • Amorphous silica nanoparticles (aSNPs) gain increasing popularity for industrial and therapeutic claims. The lung with its surface area of 1006#8211;140 m² displays an ideal target for therapeutic approaches, but it represents also a serious area of attack for harmful nanomaterials. The exact nature of the cytotoxic effects of NPs is still unknown. Furthermore, cellular pathways and the destiny of internalized NPs are still poorly understood. Therefore, we examined the cytotoxicity (MTS, LDH) and inflammatory responses (IL-8) for different-sized aSNPs (30, 70, 300 nm) on our lung epithelial cells line NCI H441 and endothelial cell line ISO-HAS-1. Additionally, colocalization studies have been conducted via immunofluorescence staining for flotillin-1- and flotillin-2-bearing endocytic vesicles. Subsequently, the relevance of flotillins concerning the viability of aSNP-exposed epithelial cells has been evaluated using flotillin-1/2 depleted cells (siRNA). This study reveals the relevanceAmorphous silica nanoparticles (aSNPs) gain increasing popularity for industrial and therapeutic claims. The lung with its surface area of 1006#8211;140 m² displays an ideal target for therapeutic approaches, but it represents also a serious area of attack for harmful nanomaterials. The exact nature of the cytotoxic effects of NPs is still unknown. Furthermore, cellular pathways and the destiny of internalized NPs are still poorly understood. Therefore, we examined the cytotoxicity (MTS, LDH) and inflammatory responses (IL-8) for different-sized aSNPs (30, 70, 300 nm) on our lung epithelial cells line NCI H441 and endothelial cell line ISO-HAS-1. Additionally, colocalization studies have been conducted via immunofluorescence staining for flotillin-1- and flotillin-2-bearing endocytic vesicles. Subsequently, the relevance of flotillins concerning the viability of aSNP-exposed epithelial cells has been evaluated using flotillin-1/2 depleted cells (siRNA). This study reveals the relevance of the nanoparticle size regarding cytotoxicity (MTS, LDH) and inflammatory responses (IL-8), whereat the smaller the size of the nanoparticle is, the more harmful are the effects. All different aSNP sizes have been incorporated in flotillin-1- and flotillin-2-labelled vesicles in lung epithelial and endothelial cells, which display a marker for late endosomal or lysosomal structures and appear to exhibit a clathrin- or caveolae-independent mode of endocytosis. Flotillin-depleted H441 showed a clearly decreased uptake of aSNPs. Additionally, the viability of aSNP-exposed cells was reduced in these cells. These findings indicate a contribution of flotillins in as yet unknown (clathrin or caveolae-independent) endocytosis mechanisms and (or) endosomal storage.zeige mehrzeige weniger

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Autor*innen:J. Kasper, M.I. Hermanns, C. Bantz, Olga Koshkina, Thomas Lang, Michael Maskos, C. Pohl, R. E. Unger, C.J. Kirkpatrick
Dokumenttyp:Zeitschriftenartikel
Veröffentlichungsform:Verlagsliteratur
Sprache:Englisch
Titel des übergeordneten Werkes (Englisch):Archives of toxicology
Jahr der Erstveröffentlichung:2012
Verlag:Springer
Verlagsort:Berlin ; Heidelberg [u.a.]
Erste Seite:1
Letzte Seite:13(?)
Freie Schlagwörter:Alveolar-capillary barrier; Cytotoxicity; Endocytosis; Endothelial cells; Flotillin-1; Flotillin-2; Inflammatory response; Lung epithelial cells; Silica nanoparticles
DOI:10.1007/s00204-012-0876-5
URL:http://link.springer.com/content/pdf/10.1007%2Fs00204-012-0876-5
ISSN:0340-5761
ISSN:1432-0738
Verfügbarkeit des Dokuments:Physisches Exemplar in der Bibliothek der BAM vorhanden ("Hardcopy Access")
Bibliotheksstandort:Sonderstandort: Publica-Schrank
Datum der Freischaltung:19.02.2016
Referierte Publikation:Ja
Datum der Eintragung als referierte Publikation:01.08.2012
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