Ambient particulate matter accelerates coagulation via an IL-6-dependent pathway

Gökhan M. Mutlu*, David Green, Amy Bellmeyer, Christina M. Baker, Zach Burgess, Nalini Rajamannan, John W. Christman, Nancy Foiles, David W. Kamp, Andrew J. Ghio, Navdeep S. Chandel, David A. Dean, Jacob I. Sznajder, G. R.Scott Budinger

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

211 Scopus citations

Abstract

The mechanisms by which exposure to particulate matter increases the risk of cardiovascular events are not known. Recent human and animal data suggest that particulate matter may induce alterations in hemostatic factors. In this study we determined the mechanisms by which particulate matter might accelerate thrombosis. We found that mice treated with a dose of well characterized particulate matter of less than 10 μM in diameter exhibited a shortened bleeding time, decreased prothrombin and partial thromboplastin times (decreased plasma clotting times), increased levels of fibrinogen, and increased activity of factor II, VIII, and X. This prothrombotic tendency was associated with increased generation of intravascular thrombin, an acceleration of arterial thrombosis, and an increase in bronchoalveolar fluid concentration of the prothrombotic cytokine IL-6. Knockout mice lacking IL-6 were protected against particulate matter-induced intravascular thrombin formation and the acceleration of arterial thrombosis. Depletion of macrophages by the intratracheal administration of liposomal clodronate attenuated particulate matter-induced IL-6 production and the resultant prothrombotic tendency. Our findings suggest that exposure to particulate matter triggers IL-6 production by alveolar macrophages, resulting in reduced clotting times, intravascular thrombin formation, and accelerated arterial thrombosis. These results provide a potential mechanism linking ambient particulate matter exposure and thrombotic events.

Original languageEnglish (US)
Pages (from-to)2952-2961
Number of pages10
JournalJournal of Clinical Investigation
Volume117
Issue number10
DOIs
StatePublished - Oct 1 2007

ASJC Scopus subject areas

  • Medicine(all)

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