Short‐term exposure to particulate matter induces arterial but not venous thrombosis in healthy mice

• Published in: Journal of thrombosis and haemostasis Vol. 8; no. 12; pp. 2651 - 2661
• Main Authors: EMMERECHTS, J., ALFARO‐MORENO, E., VANAUDENAERDE, B. M., NEMERY, B., HOYLAERTS, M. F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-12-2010
• Subjects: Air Pollutants - toxicity; air pollution; Animals; Arteries - pathology; Bronchoalveolar Lavage Fluid; coagulation; Cytokines - metabolism; Enzyme-Linked Immunosorbent Assay; inflammation; Mice; Mice, Inbred C57BL; Particle Size; particulate matter; RNA, Messenger - genetics; Thrombosis - blood; Thrombosis - etiology; Vascular Diseases - blood; Vascular Diseases - etiology; Vehicle Emissions - toxicity; Veins - pathology
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/j.1538-7836.2010.04081.x

Background:  Epidemiological findings suggest an association between exposure to particulate matter (PM) and venous thrombo‐embolism. Objectives:  To investigate arterial vs. venous thrombosis, inflammation and coagulation in mice, (sub)acutely exposed to two types of PM. Methods:  Various doses (25, 100 and 200 μg per animal) of urban particulate matter (UPM) or diesel exhaust particles (DEP) were intratracheally (i.t.) instilled in C57Bl6/n mice and several endpoints measured at 4, 10 and 24 h. Mice were also repeatedly exposed to 100 μg per animal on three consecutive days with endpoints measured 24 h after the last instillation. Results:  Exposure to 200 μg per mouse UPM enhanced arterial thrombosis, but neither UPM nor DEP significantly enhanced venous thrombosis. Both types of PM induced dose‐dependent increases in broncho‐alveolar lavage fluid (BALF) total cell numbers (mainly neutrophils) and cytokines (IL‐6, KC, MCP‐1, RANTES, MIP‐1α), with peaks at 4 h and overall higher values for UPM than for DEP. Systemic inflammation was limited to increased serum IL‐6 levels, 4 h after UPM. Both types of PM induced similar and dose‐dependent but modest increases in factor (F)VII, FVIII and fibrinogen. Three repeated instillations did not or only modestly enhance the proinflammatory and procoagulant status. Conclusions:  Compared with DEP, UPM induced more pronounced pulmonary inflammation, but both particle types triggered similar and mild short‐term systemic effects. Hence, acute exposure to PM triggers activation of primary hemostasis in the mouse, but no substantial secondary hemostasis activation, resulting in arterial but not venous thrombogenicity.