Seasonal influences on CAPs exposures: Differential responses in platelet activation, serum cytokines and xenobiotic gene expression

Fern Tablin, Laura J. Den Hartigh, Hnin Hnin Aung, Michael W. Lame, Michael J. Kleeman, Walter Ham, Jeffrey W. Norris, Monica Pombo, Dennis W Wilson

Research output: Contribution to journalArticle

10 Scopus citations

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 languageEnglish (US)
Pages (from-to)506-517
Number of pages12
JournalInhalation Toxicology
Volume24
Issue number8
DOIs
StatePublished - Jul 2012

Keywords

  • Air pollution
  • Laser capture microdissection
  • Platelet activation
  • Platelet priming
  • Serum cytokines

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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