Gökhan M. Mutlu1, David Green2, Amy Bellmeyer1, Christina M. Baker1, Zach Burgess1, Nalini Rajamannan3, John W. Christman4, Nancy Foiles2, David W. Kamp1, Andrew J. Ghio5, Navdeep S. Chandel1, David A. Dean1, Jacob I. Sznajder1 and G.R. Scott Budinger1
1Division of Pulmonary and Critical Care Medicine,
2Division of Hematology and Oncology, and
3Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
4Section of Pulmonary, Critical Care, and Sleep Medicine, University of Illinois, Chicago, Illinois, USA.
5United States Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
Address correspondence to: Gökhan M. Mutlu, Northwestern University Feinberg School of Medicine, 240 E. Huron Street, McGaw M-300, Chicago, Illinois 60611, USA. Phone: (312) 908-8163; Fax: (312) 908-4650; E-mail: firstname.lastname@example.org.
First published September 20, 2007
Received for publication October 13, 2006, and accepted in revised form July 6, 2007.
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.
An article on blood clots: http://en.wikipedia.org/wiki/Thrombosis