PMID- 25671139
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150211
LR  - 20210213
IS  - 2190-4286 (Print)
IS  - 2190-4286 (Electronic)
IS  - 2190-4286 (Linking)
VI  - 5
DP  - 2014
TI  - Proinflammatory and cytotoxic response to nanoparticles in precision-cut lung 
      slices.
PG  - 2440-9
LID - 10.3762/bjnano.5.253 [doi]
AB  - Precision-cut lung slices (PCLS) are an established ex vivo alternative to in 
      vivo experiments in pharmacotoxicology. The aim of this study was to evaluate the 
      potential of PCLS as a tool in nanotoxicology studies. Silver (Ag-NPs) and zinc 
      oxide (ZnO-NPs) nanoparticles as well as quartz particles were used because these 
      materials have been previously shown in several in vitro and in vivo studies to 
      induce a dose-dependent cytotoxic and inflammatory response. PCLS were exposed to 
      three concentrations of 70 nm monodisperse polyvinylpyrrolidone (PVP)-coated 
      Ag-NPs under submerged culture conditions in vitro. ZnO-NPs (NM110) served as 
      'soluble' and quartz particles (Min-U-Sil) as 'non-soluble' control particles. 
      After 4 and 24 h, the cell viability and the release of proinflammatory cytokines 
      was measured. In addition, multiphoton microscopy was employed to assess the 
      localization of Ag-NPs in PCLS after 24 h of incubation. Exposure of PCLS to 
      ZnO-NPs for 4 and 24 h resulted in a strong decrease in cell viability, while 
      quartz particles had no cytotoxic effect. Moreover, only a slight cytotoxic 
      response was detected by LDH release after incubation of PCLS with 20 or 30 microg/mL 
      of Ag-NPs. Interestingly, none of the particles tested induced a proinflammatory 
      response in PCLS. Finally, multiphoton microscopy revealed that the Ag-NP were 
      predominantly localized at the cut surface and only to a much lower extent in the 
      deeper layers of the PCLS. In summary, only 'soluble' ZnO-NPs elicited a strong 
      cytotoxic response. Therefore, we suggest that the cytotoxic response in PCLS was 
      caused by released Zn(2+) ions rather than by the ZnO-NPs themselves. Moreover, 
      Ag-NPs were predominantly localized at the cut surface of PCLS but not in deeper 
      regions, indicating that the majority of the particles did not have the chance to 
      interact with all cells present in the tissue slice. In conclusion, our findings 
      suggest that PCLS may have some limitations when used for nanotoxicology studies. 
      To strengthen this conclusion, however, other NP types and concentrations need to 
      be tested in further studies.
FAU - Hirn, Stephanie
AU  - Hirn S
AD  - Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universitat 
      Munchen, Marchioninistr. 15, 81377 Munich, Germany.
FAU - Haberl, Nadine
AU  - Haberl N
AD  - Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universitat 
      Munchen, Marchioninistr. 15, 81377 Munich, Germany.
FAU - Loza, Kateryna
AU  - Loza K
AD  - Inorganic Chemistry and Center of Nanointegration Duisburg-Essen (CeNIDE), 
      University of Duisburg-Essen, Universitatsstr. 5-7, 45117 Essen, Germany.
FAU - Epple, Matthias
AU  - Epple M
AD  - Inorganic Chemistry and Center of Nanointegration Duisburg-Essen (CeNIDE), 
      University of Duisburg-Essen, Universitatsstr. 5-7, 45117 Essen, Germany.
FAU - Kreyling, Wolfgang G
AU  - Kreyling WG
AD  - Institute of Epidemiology 2, Helmholtz Center Munich, Ingolstadter Landstr. 1, 
      85764 Neuherberg/Munich, Germany.
FAU - Rothen-Rutishauser, Barbara
AU  - Rothen-Rutishauser B
AD  - Adolphe Merkle Institute, Universite de Fribourg, Route de l'ancienne Papeterie 
      CP 209, 1723 Marly, Switzerland.
FAU - Rehberg, Markus
AU  - Rehberg M
AD  - Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universitat 
      Munchen, Marchioninistr. 15, 81377 Munich, Germany.
FAU - Krombach, Fritz
AU  - Krombach F
AD  - Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universitat 
      Munchen, Marchioninistr. 15, 81377 Munich, Germany.
LA  - eng
PT  - Journal Article
DEP - 20141218
PL  - Germany
TA  - Beilstein J Nanotechnol
JT  - Beilstein journal of nanotechnology
JID - 101551563
PMC - PMC4311658
OTO - NOTNLM
OT  - cytokines
OT  - cytotoxicity
OT  - ex vivo
OT  - lung slices
OT  - nanoparticles
EDAT- 2015/02/12 06:00
MHDA- 2015/02/12 06:01
PMCR- 2014/12/18
CRDT- 2015/02/12 06:00
PHST- 2014/03/19 00:00 [received]
PHST- 2014/11/25 00:00 [accepted]
PHST- 2015/02/12 06:00 [entrez]
PHST- 2015/02/12 06:00 [pubmed]
PHST- 2015/02/12 06:01 [medline]
PHST- 2014/12/18 00:00 [pmc-release]
AID - 10.3762/bjnano.5.253 [doi]
PST - epublish
SO  - Beilstein J Nanotechnol. 2014 Dec 18;5:2440-9. doi: 10.3762/bjnano.5.253. 
      eCollection 2014.