Comparison of the Biological Comparison of the Biological Effects of Sudbury Particulate Effects of Sudbury Particulate Matter (SPaM) with Other Matter (SPaM) with Other Particulate Types: Acute and Particulate Types: Acute and Chronic Studies Chronic Studies Sarah M. White Sarah M. White Stacey Ritz, PhD. Stacey Ritz, PhD.
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Comparison of the Biological Effects of Sudbury Particulate Matter (SPaM) with Other Particulate Types: Acute and Chronic Studies Sarah M. White Stacey.
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Comparison of the Biological Comparison of the Biological Effects of Sudbury Particulate Effects of Sudbury Particulate Matter (SPaM) with Other Matter (SPaM) with Other Particulate Types: Acute and Particulate Types: Acute and Chronic StudiesChronic Studies
Sarah M. WhiteSarah M. White
Stacey Ritz, PhD.Stacey Ritz, PhD.
Health Effects of Air Health Effects of Air PollutionPollution
• Mortality estimates:• 6 000 annually in Ontario (OMA)• 21 000 annually in Canada (CMA)
• Compare to breast cancer (5 300), prostate
cancer (4 300), influenza & pneumonia (8 000),
lung cancer (20 000) (StatsCan & Canadian
Cancer Society)
• 500 000 annually worldwide (WHO)
Asthma exacerbationsAsthma exacerbations Trigger for cardiovascular events in those Trigger for cardiovascular events in those
with pre-existing diseasewith pre-existing disease Exposure may facilitate the development Exposure may facilitate the development
of other disordersof other disorders Allergy Allergy AtherosclerosisAtherosclerosis Autoimmunity (?)Autoimmunity (?)
Health Effects of Air Health Effects of Air PollutionPollution
Mechanisms of Health Mechanisms of Health EffectsEffects
Oxidative stress:Oxidative stress: reactive organic compounds and transition reactive organic compounds and transition
metals involved in production of reactive oxygen metals involved in production of reactive oxygen species (ROS)species (ROS)
Inflammation:Inflammation: Release of cytokines by airway epithelial Release of cytokines by airway epithelial
cells and alveolar macrophagescells and alveolar macrophages
Particulate Matter (PM)Particulate Matter (PM)
The PM component of air pollution is The PM component of air pollution is known to have adverse health effectsknown to have adverse health effects Smaller particles are more toxicSmaller particles are more toxic
Experimental models of PM:Experimental models of PM: Diesel exhaust particles (DEPs): from a Diesel exhaust particles (DEPs): from a
diesel engine, standardizeddiesel engine, standardized Ambient particles: collected from ambient Ambient particles: collected from ambient
air, reflects local environmentair, reflects local environment
DEP DEP (Diesel exhaust Particles)(Diesel exhaust Particles)
carbon core with organic carbon core with organic compounds compounds polyaromatic hydrocarbons polyaromatic hydrocarbons
DEP makes up a DEP makes up a significantly large portion of significantly large portion of PMPM Depends on local contributors to PMDepends on local contributors to PM Mostly fine and ultrafine in sizeMostly fine and ultrafine in size
Standardized DEP is widely used Standardized DEP is widely used in experimental settings (cell in experimental settings (cell culture, animal studies, human culture, animal studies, human studies)studies)
Transmission electron microscopy image of DEP http://www.transportation.anl.gov/engines/diesel_structure.html
EHC-93EHC-93
Ambient urban sample from Ottawa ONAmbient urban sample from Ottawa ON Bronchial epithelial cells exposed to Bronchial epithelial cells exposed to
EHC-93 upregulate expression of EHC-93 upregulate expression of inflammatory cytokinesinflammatory cytokines GM-CSF, IL-8 and IL-1 (Fujii et al, 2001)GM-CSF, IL-8 and IL-1 (Fujii et al, 2001)
Used in numerous cell culture and animal Used in numerous cell culture and animal modelsmodels
Collected by Kati Collected by Kati McCartney of the Ritz McCartney of the Ritz lab in 2006 lab in 2006
Reflects local Reflects local environment in Sudbury, environment in Sudbury, which is impacted by which is impacted by local industrial activitieslocal industrial activities
Image of the particulate collected from one filter (McCartney, 2009)
Transition Metal Content Transition Metal Content of PM Samplesof PM Samples
(McCartney ,2009)(McCartney ,2009)
Hypothesis Hypothesis
• Ambient PM samples will elicit greater
inflammatory effects than DEPs• Transition metal content
• Tested in 3 experimental settings:• Cell cultures (bronchial epithelial cells)• Acute exposure in mice• Chronic exposure in mice
Cell Culture: ALICell Culture: ALI Previous work by McCartney et al indicated that Previous work by McCartney et al indicated that
exposure to SPaM elicited enhanced pro-inflammatory exposure to SPaM elicited enhanced pro-inflammatory cytokine production (IL-8) in cells grown under cytokine production (IL-8) in cells grown under standard conditionsstandard conditions
BEAS2B cells were grown in ALI (Air Liquid Interface) BEAS2B cells were grown in ALI (Air Liquid Interface) cell culture to better model cell culture to better model in vivoin vivo..
IL-8 production by airway epithelial IL-8 production by airway epithelial cells after PM exposurecells after PM exposure
IL-8 concentrations in Particulate Matter treated BEASE2B Cells in ALI Culture
0
5
10
15
20
25
30
35
40
45
50
Control DEP EHC-93 SPaM
Particulate Matter treatment (50ug)
IL-8
Co
ncen
trati
on
in
(p
g/m
L)
(ANOVA on Ranks P=0.017)
Acute StudyAcute Study
Balb/c mice exposed to 250ug of Balb/c mice exposed to 250ug of PM via intranasal instillationPM via intranasal instillation Background exposure to PM Background exposure to PM
reduced by specialized caging reduced by specialized caging systemsystem
Mice euthanized at 12h post-Mice euthanized at 12h post-exposureexposure Airway inflammationAirway inflammation Acute phase responseAcute phase response
Airway Neutrophilia after Airway Neutrophilia after acute exposure to PMacute exposure to PM
(ANOVA P=0.006)
Control
DEP
EHC-93
SPaM
Chronic StudyChronic Study Balb/c mice exposed to aerosolized Balb/c mice exposed to aerosolized
suspensions of PM in chamberssuspensions of PM in chambers 15 min a day, five days a week15 min a day, five days a week Concentration of aerosol in chamber is 400ug/mConcentration of aerosol in chamber is 400ug/m33 estimated dose of 24 ug/kg/week estimated dose of 24 ug/kg/week
Comparable to ambient exposure in typical urban areaComparable to ambient exposure in typical urban area
Neutrophilic Airway Neutrophilic Airway Inflammation During Chronic Inflammation During Chronic ExposureExposure
Percentage of Neutrophils found in BAL from PM Treated Balb/c mice
0
1
2
3
4
5
6
7
8
9
Control DEP EHC SPaM
Treatment Group
Per
cen
tag
e o
f N
eutr
op
hils
2 weeks4 weeks6 weeks
Implications Implications
The acute study reinforces the need for The acute study reinforces the need for occupational health and safety for workers who occupational health and safety for workers who can be exposed to large doses of PM. can be exposed to large doses of PM. There was signs of inflammation in all PM treated There was signs of inflammation in all PM treated
groups groups
The chronic study shows some evidence of The chronic study shows some evidence of physiological changes in the respiratory epithelium physiological changes in the respiratory epithelium
AcknowledgementsAcknowledgements
Special thanks to all the members of Team Ritz:Special thanks to all the members of Team Ritz: Kati McCartney, Cathy Brummer, Jane Bulloch, Nya Fraleigh, Kati McCartney, Cathy Brummer, Jane Bulloch, Nya Fraleigh,