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Enhanced peripheral thrombogenicity after lung inflammation is mediated by platelet-leukocyte activation: role of P-selectin

Nemmar, A and Hoet, P. H. M. and Vandervoort, P and Dinsdale, D and Nemery, B and Hoylaerts, M. F. (2007) Enhanced peripheral thrombogenicity after lung inflammation is mediated by platelet-leukocyte activation: role of P-selectin. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 5 (6). pp. 1217-1226.

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Official URL: http://www.ingentaconnect.com/content/bsc/jth/2007...

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 mu g 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.

Item Type:Article
Uncontrolled Keywords:carbon nanotubes; inflammation; leukocytes; P-selectin; thrombosis
Subjects:Risk > Environment, health and safety aspects of nanotechnology
Biomedical Science > Nanotechnology for human health
ID Code:770
Deposited By:Farnush Anwar
Deposited On:15 Dec 2008 10:42
Last Modified:19 Feb 2009 17:40

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