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.
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.
Authors: Leslie C Thompson; Rakhee N Urankar; Nathan A Holland; Achini K Vidanapathirana; Joshua E Pitzer; Li Han; Susan J Sumner; Anita H Lewin; Timothy R Fennell; Robert M Lust; Jared M Brown; Christopher J Wingard Journal: Toxicol Sci Date: 2014-01-15 Impact factor: 4.849
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Authors: Mark R Miller; Steven G McLean; Rodger Duffin; Akeem O Lawal; Jesus A Araujo; Catherine A Shaw; Nicholas L Mills; Ken Donaldson; David E Newby; Patrick W F Hadoke Journal: Part Fibre Toxicol Date: 2013-12-11 Impact factor: 9.400
Authors: Caroline M Tabor; Catherine A Shaw; Sarah Robertson; Mark R Miller; Rodger Duffin; Ken Donaldson; David E Newby; Patrick W F Hadoke Journal: Part Fibre Toxicol Date: 2016-02-09 Impact factor: 9.400