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

• Published in: Journal of thrombosis and haemostasis Vol. 5; no. 6; pp. 1217 - 1226
• Main Authors: NEMMAR, A., HOET, P. H. M., VANDERVOORT, P., DINSDALE, D., NEMERY, B., HOYLAERTS, M. F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-06-2007
• Subjects: Animals; Blood Platelets - physiology; carbon nanotubes; Disease Models, Animal; Female; Granulocytes - physiology; inflammation; leukocytes; Leukocytes - physiology; Male; Mice; Nanotubes, Carbon - toxicity; P-Selectin - blood; Platelet Activation; Pneumonia - blood; Pneumonia - complications; Pneumonia - etiology; P‐selectin; Thromboplastin - biosynthesis; thrombosis; Thrombosis - blood; Thrombosis - etiology
• DOI: 10.1111/j.1538-7836.2007.02557.x
• EISSN: 1538-7836
• ISSN: 1538-7933; 1538-7836

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 μg 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.