pulmonary effects of engineered nanoparticles
DESCRIPTION
Pulmonary Effects of Engineered Nanoparticles. Hasan Bayram MD,PhD. Department of Respiratory Medicine, School of Medicine, University of Gaziantep E-mail: bayram@gantep . edu.tr. TTS 14 th Annual Congresss, Antalya 13-17 April 2011. Conflicts of Interest. - PowerPoint PPT PresentationTRANSCRIPT
Pulmonary Effects of Engineered Nanoparticles
Hasan Bayram MD,PhD.
Department of Respiratory Medicine, School of Medicine, University of Gaziantep
E-mail: [email protected]
TTS 14th Annual Congresss, Antalya 13-17 April 2011.
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Conflicts of Interest• Abdi Ibrahim Drug Company sponsored
my attendance at international congresses twice in 2008 and 2010.
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PubMed Publications: “Nanoparticles” AND “Lung” AND “Toxicity”
Publications
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Content• Nanoparticles entering the lung and the cell• Histopathological and inflammatory changes• Interaction with allergens and LPS• Effects of cell permeability and toxic parameters• Effects on cell viability, apoptosis, cell cycle (cell
lines, primary cells, COPD cells)• Signaling pathways, transcriptional effects• Effects on oxidative stress• Summary
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Nanopartcle Application at Experimental Settings
• Pharyngeal aspiration
• Intra-tracheal instillation
• Inhalation of aerosols
• Exposure to freshly generated nanoparticles
• Oral application
• Intraarticular injection
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MWCNT in the Conducting Airways
ciliaMWCNT
MWCNT
Courtesy of John Howard, NIOSH
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MAKFJPARK
BRONCHİOL
Ryman-Rasmussen JP et al. AJRCMB, 2009 .
MWCNT Distribution in Lung Tissue of Mice 1d After Inhalation of Aerosol (100mg/m3) for 6hrs
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Migration of MWCNTs from Lung: Pleural Penetration
Courtesy of John Howard, NIOSH
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Polystyrene Nanoparticle Trafficking Across Alveolar epithelium
Yacobi NR et al, 2008
1010
Effects of Pharyngeal Aspiration of Single Wall Carbon Nanotube on Respiratory Tract in Mice
Shvedova AA et al, 2005
1 day post exposure 40 g/mouse SWCNT
28 days post exposure 40 g/mouse SWCNT
20 microns 20 microns
Acute inflammation and fibrosis Granulomas
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Percentage of Neutrophils in Lung Lavage of Rats and Mice 24 hr After Intratracheal Instillation
Oberdörster G et al, 2005
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Effects of Titanium Dioxide Nanoparticles (TNP, 20/mg/kg) on Cytokine Levels in BAL After a
Single Intratracheal Instillation
Park EJ et al. Toxicology. 2009
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TiO2 Particles Coated with Silica Induce Level of BAL Cells of Mice Following 2h, 2h/4d, 2h/4wks
Exposure
Rossi FM et al, Toxicol Sci. 2010
A=2hrsB=2hrs/4dysC=2hrs/4wks
• CXCL1 and TNF-α mRNA levels increased
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Effects of Multi-walled Carbon Nanotubes (100nm; 0.4mg/ml) on Cytokine Release From Human Keratinocytes
Witzmann FA et al, 2006
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Effect of 300µg/ml cnTiO2 on Expression of TNF-α and CXCL 1 mRNA in Human Macrophages after 3-24hrs
Rossi FM et al, Toxicol Sci. 2010
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Effects of Inhaled TiO2 Particles (42mg/m3,11days) on microRNA Expression in Lungs of Mice
Halappanavar S, et al. Environ Mol Mutagen. 2011
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Effects of Gold NPs ± LPS on Gene Expression of TNF-α, IL-8 and iNOS in a Triple-Culture Model of Macrophages, A549 and Dentritic
Cells
•No effect on inflammatory and anti-inflammatory cytokine release, either.
Brandenberger C, et al. Toxicol Appl Pharmacol, 2010.
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Effects of Titanium Dioxide Nanoparticles (TNP, 20/mg/kg) on Levels of IgE in BAL and Blood After
a Single Intratracheal Instillation
Park EJ et al. Toxicology. 2009
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IL-13 mRNA and Protein Levels at 1d After MWCNT Inhalation
Ryman-Rasmussen JP et al. AJRCMB, 2009 .
• Protein levels of PDGF and TGF-β1, • mRNA levels of IL-5, CCL2/MCP-1, CCL11/eotaxin and CXCL9 were increased by OVA + MWCNT
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Lung Histopathology in Rats Exposed to MWCNT for 21d (blue indicates collagen).
MWCNT MWCNT + LPS
Cesta MF et al. AJRCMB’09
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Effects of CB or MWCNT on Lung Injury
Cesta MF et al. AJRCMB’09
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Tight Junction Expression and Transepithelial Electrical Resistance of A549 Cells
Rothen-Rutishauser B et al. Environ Sci Technol. 2009
10’=12µg/cm2
20’=19µg/cm2
30’=24µg/cm2
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Effects of Zinc Oxide NPs on Electrical Resistance (RT) of Rat Alveolar Epithelial Cell Cultures
Kim YH, et al. AJRCCM 2010.
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Effects of Zinc Oxide NPs on Lactate Dehydrogenase Release from Rat Alv. Epithelial Cell Cultures
Kim YH, et al. AJRCCM 2010.
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Effects of Tungsten Carbide (WC) and Cobalt-doped Tungsten Carbide (WC-Co) NPs on Viability of Mammalian Cells.
Bastian S et al, 2009.
Human Keratinocyte Cells A549 Alveolar-epithelial Cells
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Effects of TiO2 and MWCNT on BEAS-2B Cell Viability
0 3 10 30 100
300
0.0
0.5
1.0
*
*
*p<0,0001
TiO
224. hour
Op
tica
l D
ensi
ty
0 3 10 30 100
300
0.0
0.5
1.0
1.5
*
*p<0,0001
*
48. Hour
0 3 10 30 100
300
0.0
0.2
0.4
0.6
0.8
1.0
MW
CN
T
*p<0.0001
* *
(g/ml)
Op
tica
l D
ensi
ty
0 3 10 30 100
300
0.0
0.2
0.4
0.6
0.8
1.0*p<0,0001
**
(g/ml)
Op
tica
l D
ensi
ty
Gögebakan B, et al. TTS Congress, 2011.
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Effects of TiO2 on Viability of Bronchial Epithelial Cells from Smokers and COPD Patients
0 3 10 30 100 3000
1
2
3
*
#*p<0,0001#p<0,0001
*
SM
OK
ER
S24. Hour
Op
tica
l D
ensi
ty
0 3 10 30 100 3000.0
0.5
1.0
1.5
2.0
2.5
48. Hour
0 3 10 30 100 3000.0
0.5
1.0
1.5
2.0
2.5*p<0,001**p=0,0016
CO
PD
TiO2 (g/ml)
** ** ** *
Op
tica
l D
ensi
ty
0 3 10 30 100 3000.0
0.5
1.0
1.5
2.0
*
*p<0,001
* *
TiO2 (g/ml)
Gögebakan B, et al. TTS Congress, 2011.
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Effects of MWCNT on Viability of Bronchial Epithelial Cells from Smokers and COPD Patients
0 3 10 30 100 3000.0
0.5
1.0
1.5
**
*p<0,0001
SM
OK
ER
S24. Hour
Op
tica
l D
ensi
ty
0 3 10 30 100 3000.0
0.5
1.0
1.5
**
*p<0,0001
48. Hour
0 3 10 30 100 3000.0
0.5
1.0
1.5
*
*p=0,0418
CO
PD
MWCNT (g/ml)
Op
tica
l D
ensi
ty
0 3 10 30 100 3000.0
0.2
0.4
0.6
0.8
1.0
* * *
*p=0,0068
MWCNT (g/ml)
Gögebakan B, et al. TTS Congress, 2011.
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Effects of 48h Incubation With TiO2 and MWCNT on BEAS-2B Cell Apoptosis
LL LL LR LR UR UR UL UL0
2
4
6
885
90
95
100
*
*p= 0,0009**p=0,0169
*
**
SF (0g/ml TiO2)
300 g/ml TiO2
Viable Early Apo Late Apo Necrotic
Cel
ls %
LL LL LR LR UR UR UL UL
0
5
10
1575
80
85
90
95
100
*
*p<0,0001**p=0,0003***p<0,0001
*****
SF (0g/ml MWCNT)
300 g/ml MWCNT
Viable Early Apo Late Apo Necrotic
Cel
ls %
TiO2MWCNT
Gögebakan B, et al. TTS Congress, 2011.
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Effects of Single-walled Carbon Nanotubes and C(60) Fullerenes on Cell Cycle of Mouse Lung Epithelial Cells
Jacobsen NR et al, 2008
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Effects of 100µg/ml Polyamidoamine Dendrimer(PAMAM) Nanoparticles and 3-Methyladenine (Autophay Inhb.)
on Autophagy in A549 Cells After 24hrs
Li FT et al. J Mol Cell Biol. 2009 autophagosomes
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Effects of Different Sized CeO2 Nanoparticles on pERK, p38 and pJNK in BEAS-2B Cells after 24 h
Eom HJ et al. Toxicol Lett. 2009
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Expressions of NF-B, I-B and Nrf-2 in Cytosolic and Nuclear Fractions of BEAS-2B Cells Exposed to Different
Sized CeO2 Nanoparticles for 24h.
Eom HJ et al. Toxicol Lett. 2009
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Effect of ZnO on Expression of IL-8 mRNA in Human BECs
Wu W, et al. EHP, 2010
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Effect of ZnO Nanoparticles ± NAC, on IntracellularCalcium Concentrations
Huang CC et al. Toxicol In Vitro. 2009
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Effects of 20µg/cm2 Carbon Black and TiO2 NPs on Caspase 8 and Caspase 3/7 Activity in 16HBE14o- cells
Hussain S, et al. Part Fibre Toxicol. 2010
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Non-cellular Nanoparticle ROS Activity
Elder A, et al 2008 (http://www.epa.gov)
Surface AreaParticle Mass
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Effects of Cerium Oxide NPs (30nm) on ROS Induction in BEAS-2B Cells.
Park EJ et al, 2008
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Summary• Nanoparticles enter into airways, parenchyme, cells• Causes collagen deposition, fibrosis, granuloma,
inflammation• Modulate allergic response, synergism with LPS• Increases in epithelial permeability• Decreases in cell viability and cell cycle progression,
increases in apoptosis and autophagy• Diseased cells (COPD) may be more susceptible• Activation of signaling mechanism and transcription
factors that are sensitive to oxidative stress• ROS formation and induce oxidative stress
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Acknowledgements
Prof. Günter Oberdörster
Director, University of Rochester Ultrafine Particle
Center
Thank You for Your [email protected]