Factor XII activation is essential to sustain the procoagulant effects of particulate matter

Kilinc E., Van Oerle R., Borissoff J. I., Oschatz C., Gerlofs-Nijland M. E., Janssen N. A., ...More

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, vol.9, no.7, pp.1359-1367, 2011 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 9 Issue: 7
  • Publication Date: 2011
  • Doi Number: 10.1111/j.1538-7836.2011.04280.x
  • Journal Name: JOURNAL OF THROMBOSIS AND HAEMOSTASIS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED)
  • Page Numbers: pp.1359-1367
  • Keywords: air pollution, blood coagulation, factor XII, intrinsic coagulation pathway, particulate matter, thrombin generation, AIR-POLLUTION, ULTRAFINE PARTICLES, EXTRAPULMONARY TRANSLOCATION, LUNG INFLAMMATION, IN-VIVO, CARDIOVASCULAR-DISEASE, COAGULATION-FACTORS, THROMBUS FORMATION, EXPOSURE, INHALATION
  • Acibadem Mehmet Ali Aydinlar University Affiliated: No

Abstract

Background: Particulate matter (PM) is a key component of ambient air pollution and has been associated with an increased risk of thrombotic events and mortality. The underlying mechanisms remain unclear. Objectives: To study the mechanisms of PM-driven procoagulant activity in human plasma and to investigate mainly, the coagulation driven by ultrafine particles (UFPs; < 0.1 mu m) in genetically modified mice. Methods: Thrombin generation in response to PM of different sizes was assessed in normal human platelet-poor plasma, as well as in plasmas deficient in the intrinsic pathway proteases factors XII (FXII) or XI (FXI). In addition, UFPs were intratracheally instilled in wild-type (WT) and FXII-deficient (FXII(-/-)) mice and plasma thrombin generation was analyzed in plasma from treated mice at 4 and 20 h post-exposure. Results: In normal human plasma, thrombin generation was enhanced in the presence of PM, where as PM-driven thrombin formation was completely abolished in FXII-and FXI-deficient plasma. UFPs induced a transient increase in tissue factor (TF)-driven thrombin formation at 4 h post-instillation in WT mice compared with saline instillation. Intratracheal instillation of UFPs resulted in a procoagulant response in WT mice plasma at 20 h, whereas it was entirely suppressed in FXII(-/-) mice. Conclusions: Overall, the data suggest that PM promotes its early procoagulant actions mostly through the TF-driven extrinsic pathway of coagulation, whereas PM-driven long lasting thrombogenic effects are predominantly mediated via formation of activated FXII. Hence, FXII-driven thrombin formation may be relevant to an enhanced thrombotic susceptibility upon chronic exposure to PM in humans.