ORIGINAL ARTICLE

The procoagulant potential of environmental particles (PM₁₀)

P S Gilmour¹, E R Morrison², M A Vickers², I Ford², C A Ludlam³, M Greaves², K Donaldson¹, W MacNee¹

¹ Edinburgh Lung and the Environment Group Initiative (ELEGI)/Colt Laboratory, The University of Edinburgh, Department of Medicine and Radiological Sciences, Medical school, Wilkie Building, Teviot Place, Edinburgh, UK
² Haematology Unit, Department of Medicine and Therapeutics, Polwarth Building, Medical School, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
³ Department of Haematology, Royal Infirmary of Edinburgh, Old Dalkeith Road, Edinburgh, UK

Correspondence to:
Correspondence to:
Prof. W MacNee
ELEGI/Colt Laboratory, The University of Edinburgh, Wilkie Building, Medical School, Teviot Place, Edinburgh EH8 9AG, UK; w.macnee{at}ed.ac.uk

Background and Aims: Epidemiology studies have shown that cardiovascular (CV) disease is primarily responsible for the mortality associated with increased pulmonary environmental particle (PM₁₀) exposure. The mechanisms involved in PM₁₀ mediated CV effects are unknown although changes in plasma viscosity and in the homoeostasis of blood coagulation have been implicated. It was hypothesised that PM₁₀ exposure would result in an inflammatory response and enhance the activation of the extrinsic coagulation mechanisms in pulmonary and vascular cells in culture.

Methods: Primary human monocyte derived macrophages and human umbilical cord vein endothelial, human alveolar type II epithelial (A549), and human bronchial epithelial (16HBE) cells were tested for their inflammatory and procoagulant response to PM₁₀ exposure. IL-8, tissue factor (TF), and tissue plasminogen activator (tPA) gene expression and protein release, and coagulation enhancing ability of culture media were determined 6 and 24 hours following exposure.

Results: The culture media from macrophages and 16HBE bronchial epithelial cells, but not A549 cells, exposed to PM₁₀ had an enhanced ability to cause clotting. Furthermore, H₂O₂ also increased the clotting activity. Apoptosis was significantly increased in macrophages exposed to PM₁₀ and LPS as shown by annexin V binding. TF gene expression was enhanced in macrophages exposed to PM₁₀, and HUVEC tissue factor and tPA gene and protein expression were inhibited.

Conclusions: These data indicate that PM₁₀ has the ability to alter macrophage, epithelial, and endothelial cell function to favour blood coagulation via activation of the extrinsic pathway and inhibition of fibrinolysis pathways.

Abbreviations: ARDS, adult respiratory distress syndrome; COPD, chronic obstructive pulmonary disease; CV, cardiovascular; HBE, human bronchial epithelial; HUVEC, human umbilical vein endothelial cell; IL, interleukin; LPS, lipopolysaccharide; PAI, plasminogen activator inhibitor; PM, particulate matter; TF, tissue factor; TNF, tumour necrosis factor; tPA, tissue plasminogen activator

Keywords: PM10; cardiovascular; thrombosis; inflammation

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