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

A. Nemmar, P. H.M. Hoet, P. Vandervoort, D. Dinsdale, B. Nemery, Marc F. Hoylaerts

Research output: Contribution to journalArticlepeer-review

83 Citations (Scopus)

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 μg of multiwall ground CNTs triggered substantial lung neutrophil, but not macrophage influx, 24 h later. The detection of circulating platelet-leukocyte conjugates exclusively 6h 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.

Original languageEnglish
Pages (from-to)1217-1226
Number of pages10
JournalJournal of Thrombosis and Haemostasis
Volume5
Issue number6
DOIs
Publication statusPublished - Jun 1 2007
Externally publishedYes

Keywords

  • Carbon nanotubes
  • Inflammation
  • Leukocytes
  • P-selectin
  • Thrombosis

ASJC Scopus subject areas

  • Hematology

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