Title: Enhanced peripheral thrombogenicity after lung inflammation is mediated by platelet-leukocyte activation: role of P-selectin
Authors: Nemmar, A
Hoet, Peter
Vandervoort, Petra
Dinsdale, D
Nemery, Benoit
Hoylaerts, Marc # ×
Issue Date: Jun-2007
Publisher: Blackwell Pub.
Series Title: Journal of Thrombosis and Haemostasis vol:5 issue:6 pages:1217-1226
Abstract: BACKGROUND: Inhaled ultrafine particles trigger peripheral thrombotic complications. METHODS: We have analyzed the systemic prothrombotic risk following lung inflammation induced by pulmonary carbon nanotubes (CNTs). RESULTS: Intratracheal instillation in Swiss mice of 200 and 400 microg of multiwall ground CNTs triggered substantial lung neutrophil, but not macrophage influx, 24 h later. The detection of circulating platelet-leukocyte conjugates exclusively 6 h after CNT instillation pointed to early but transient activation of circulating platelets. At 24 h, elevated plasma procoagulant microvesicular tissue factor activity was found in CNT-exposed but not in saline-exposed mice. However, at 24 h, both the tail and jugular vein bleeding times were prolonged in CNT-exposed but not in saline-exposed mice, arguing against strong CNT-induced platelet activation at this point. Nevertheless, at 24 h, enhanced peripheral thrombogenicity was detected in CNT-exposed but not in saline-exposed mice, via quantitative photochemically induced carotid artery thrombosis measurements. P-selectin neutralization abrogated platelet-leukocyte conjugate formation and microvesicular tissue factor generation, and abolished the CNT-induced thrombogenicity amplification. In contrast, the weak vascular injury-triggered thrombus formation in saline-treated mice was not affected by P-selectin neutralization at 24 h. CONCLUSIONS: The mild CNT-induced lung inflammation translates via rapid but mild and transient activation of platelets into P-selectin-mediated systemic inflammation. Leukocyte activation leads to tissue factor release, in turn eliciting inflammation-induced procoagulant activity and an associated prothrombotic risk.
ISSN: 1538-7933
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Environment and Health - miscellaneous
Molecular and Vascular Biology
Occupational, Environmental and Insurance Medicine (-)
× corresponding author
# (joint) last author

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