Exposure of mice to concentrated ambient particulate matter results in platelet and systemic cytokine activation

Dennis W Wilson, H. H. Aung, M. W. Lame, L. Plummer, Kent E Pinkerton, W. Ham, M. Kleeman, J. W. Norris, Fern Tablin

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Increasingly, evidence suggests a role for a systemic procoagulant state in the pathogenesis of cardiac dysfunction subsequent to inhalation of airborne particulate matter. The authors evaluated blood cell parameters and markers of platelet activation in mice exposed to concentrated ambient particulate matter (CAPs) from the San Joaquin Valley of California, a region with severe particulate matter (PM) pollution episodes. The authors exposed mice to an average of 88.5 μg/m3 of CAPs 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, aggregation, fibrinogen binding, P-selectin, and lysosomal-associated membrane protein-1 (LAMP-1) expression. Serum cytokines were analyzed by bead-based immunologic assays. CAPs-exposed mice had elevations in macrophage inflammatory protein (MIP)-1α, MIP-1β, interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNFα), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor (PDGF)-bb, and RANTES (regulated upon activation, normally T-expressed, and presumably secreted). Platelets were the only peripheral blood cells that were significantly elevated in number in CAPs-exposed mice. Flow cytometric analysis of unstimulated platelets from CAPs-exposed mice indicated size and shape changes, and platelets from CAPs-exposed animals had a 54% increase in fibrinogen binding indicative of platelet priming. Stimulation of platelets by thrombin resulted in up-regulation of LAMP-1 expression in CAPs-exposed animals and an increased microparticle population relative to control animals. These findings demonstrate a systemic proinflammatory and procoagulant response to inhalation of environmentally derived fine and ultrafine PM and suggests a role for platelet activation in the cardiovascular and respiratory effects of particulate air pollution.

Original languageEnglish (US)
Pages (from-to)267-276
Number of pages10
JournalInhalation Toxicology
Volume22
Issue number4
DOIs
StatePublished - Mar 2010

Keywords

  • Air pollution
  • Cytokines
  • Flow cytometry
  • Platelet activation
  • Platelets

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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