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

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 mu g per animal) of urban particulate matter (UPM) or diesel exhaust particles (DEP) were intratracheally (i.t.) instilled in C57B16/n mice and several endpoints measured at 4, 10 and 24 h. Mice were also repeatedly exposed to 100 mu g per animal on three consecutive days with endpoints measured 24 h after the last instillation. Results: Exposure to 200 mu g 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-1 alpha), 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.