Abstract
Increasing evidence suggests a role for a systemic pro-coagulant state in the pathogenesis of cardiac dysfunction subsequent to inhalation of airborne particulate matter (PM). We evaluated platelet activation, systemic cytokines and pulmonary gene expression in mice exposed to concentrated ambient particulate matter (CAPs) in the summer of 2008 (S08) and winter of 2009 (W09) from the San Joaquin Valley of California, a region with severe PM pollution episodes. Additionally, we characterized the PM from both exposures including organic compounds, metals, and polycyclic aromatic hydrocarbons. Mice were exposed to an average of 39.01 μg/m of CAPs in the winter and 21.7 μg/m3 CAPs in the summer, in a size range less than 2.5 μm for 6h/day for 5 days per week for 2 weeks. Platelets were analyzed by flow cytometry for relative size, shape, CD41, P-selectin and lysosomal associated membrane protein-1 (LAMP-1) expression. Platelets from W09 CAPs-exposed animals had a greater response to thrombin stimulation than platelets from S08 CAPs-exposed animals. Serum cytokines were analyzed by bead based immunologic assays. W09 CAPs-exposed mice had elevations in IL-2, MIP-1α, and TNFα. Laser capture microdissection (LCM) of pulmonary vasculature, parenchyma and airways all showed increases in CYP1a1 gene expression. Pulmonary vasculature showed increased expression of ICAM-1 and Nox-2. Our findings demonstrate that W09 CAPs exposure generated a greater systemic pro-inflammatory and pro-coagulant response to inhalation of environmentally derived fine and ultrafine PM. Changes in platelet responsiveness to agonists, seen in both exposures, strongly suggests a role for platelet activation in the cardiovascular and respiratory effects of particulate air pollution.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 506-517 |
| Number of pages | 12 |
| Journal | Inhalation Toxicology |
| Volume | 24 |
| Issue number | 8 |
| DOIs | |
| State | Published - Jul 2012 |
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Keywords
- Air pollution
- Laser capture microdissection
- Platelet activation
- Platelet priming
- Serum cytokines
ASJC Scopus subject areas
- Toxicology
- Health, Toxicology and Mutagenesis
Cite this
Seasonal influences on CAPs exposures : Differential responses in platelet activation, serum cytokines and xenobiotic gene expression. / Tablin, Fern; Den Hartigh, Laura J.; Aung, Hnin Hnin; Lame, Michael W.; Kleeman, Michael J.; Ham, Walter; Norris, Jeffrey W.; Pombo, Monica; Wilson, Dennis W.
In: Inhalation Toxicology, Vol. 24, No. 8, 07.2012, p. 506-517.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Seasonal influences on CAPs exposures
T2 - Differential responses in platelet activation, serum cytokines and xenobiotic gene expression
AU - Tablin, Fern
AU - Den Hartigh, Laura J.
AU - Aung, Hnin Hnin
AU - Lame, Michael W.
AU - Kleeman, Michael J.
AU - Ham, Walter
AU - Norris, Jeffrey W.
AU - Pombo, Monica
AU - Wilson, Dennis W
PY - 2012/7
Y1 - 2012/7
N2 - Increasing evidence suggests a role for a systemic pro-coagulant state in the pathogenesis of cardiac dysfunction subsequent to inhalation of airborne particulate matter (PM). We evaluated platelet activation, systemic cytokines and pulmonary gene expression in mice exposed to concentrated ambient particulate matter (CAPs) in the summer of 2008 (S08) and winter of 2009 (W09) from the San Joaquin Valley of California, a region with severe PM pollution episodes. Additionally, we characterized the PM from both exposures including organic compounds, metals, and polycyclic aromatic hydrocarbons. Mice were exposed to an average of 39.01 μg/m of CAPs in the winter and 21.7 μg/m3 CAPs in the summer, in a size range less than 2.5 μm for 6h/day for 5 days per week for 2 weeks. Platelets were analyzed by flow cytometry for relative size, shape, CD41, P-selectin and lysosomal associated membrane protein-1 (LAMP-1) expression. Platelets from W09 CAPs-exposed animals had a greater response to thrombin stimulation than platelets from S08 CAPs-exposed animals. Serum cytokines were analyzed by bead based immunologic assays. W09 CAPs-exposed mice had elevations in IL-2, MIP-1α, and TNFα. Laser capture microdissection (LCM) of pulmonary vasculature, parenchyma and airways all showed increases in CYP1a1 gene expression. Pulmonary vasculature showed increased expression of ICAM-1 and Nox-2. Our findings demonstrate that W09 CAPs exposure generated a greater systemic pro-inflammatory and pro-coagulant response to inhalation of environmentally derived fine and ultrafine PM. Changes in platelet responsiveness to agonists, seen in both exposures, strongly suggests a role for platelet activation in the cardiovascular and respiratory effects of particulate air pollution.
AB - Increasing evidence suggests a role for a systemic pro-coagulant state in the pathogenesis of cardiac dysfunction subsequent to inhalation of airborne particulate matter (PM). We evaluated platelet activation, systemic cytokines and pulmonary gene expression in mice exposed to concentrated ambient particulate matter (CAPs) in the summer of 2008 (S08) and winter of 2009 (W09) from the San Joaquin Valley of California, a region with severe PM pollution episodes. Additionally, we characterized the PM from both exposures including organic compounds, metals, and polycyclic aromatic hydrocarbons. Mice were exposed to an average of 39.01 μg/m of CAPs in the winter and 21.7 μg/m3 CAPs in the summer, in a size range less than 2.5 μm for 6h/day for 5 days per week for 2 weeks. Platelets were analyzed by flow cytometry for relative size, shape, CD41, P-selectin and lysosomal associated membrane protein-1 (LAMP-1) expression. Platelets from W09 CAPs-exposed animals had a greater response to thrombin stimulation than platelets from S08 CAPs-exposed animals. Serum cytokines were analyzed by bead based immunologic assays. W09 CAPs-exposed mice had elevations in IL-2, MIP-1α, and TNFα. Laser capture microdissection (LCM) of pulmonary vasculature, parenchyma and airways all showed increases in CYP1a1 gene expression. Pulmonary vasculature showed increased expression of ICAM-1 and Nox-2. Our findings demonstrate that W09 CAPs exposure generated a greater systemic pro-inflammatory and pro-coagulant response to inhalation of environmentally derived fine and ultrafine PM. Changes in platelet responsiveness to agonists, seen in both exposures, strongly suggests a role for platelet activation in the cardiovascular and respiratory effects of particulate air pollution.
KW - Air pollution
KW - Laser capture microdissection
KW - Platelet activation
KW - Platelet priming
KW - Serum cytokines
UR - http://www.scopus.com/inward/record.url?scp=84863317134&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863317134&partnerID=8YFLogxK
U2 - 10.3109/08958378.2012.695815
DO - 10.3109/08958378.2012.695815
M3 - Article
C2 - 22746400
AN - SCOPUS:84863317134
VL - 24
SP - 506
EP - 517
JO - Inhalation Toxicology
JF - Inhalation Toxicology
SN - 0895-8378
IS - 8
ER -