title: Ambient particulate matter accelerates coagulation via an IL-6-dependent pathway.
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 microM 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.
authors: Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. g-mutlu@northwestern.edu
authors: Gökhan M
authors: GM
authors: Mutlu
authors: David
authors: D
authors: Green
authors: Amy
authors: A
authors: Bellmeyer
authors: Christina M
authors: CM
authors: Baker
authors: Zach
authors: Z
authors: Burgess
authors: Nalini
authors: N
authors: Rajamannan
authors: John W
authors: JW
authors: Christman
authors: Nancy
authors: N
authors: Foiles
authors: David W
authors: DW
authors: Kamp
authors: Andrew J
authors: AJ
authors: Ghio
authors: Navdeep S
authors: NS
authors: Chandel
authors: David A
authors: DA
authors: Dean
authors: Jacob I
authors: JI
authors: Sznajder
authors: G R Scott
authors: GR
authors: Budinger
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000235:genetics*; D001779:Blood Coagulation Factors / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002341:Carotid Artery Thrombosis / Q000139:chemically induced* / Q000235:genetics*; D002712:Chlorides; D004002:Clodronic Acid / Q000008:administration & dosage; D005290:Ferric Compounds / Q000633:toxicity; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D052638:Particulate Matter / Q000633:toxicity*; D011517:Prothrombin Time; D013917:Thrombin / Q000378:metabolism
chemical_list: D001779:Blood Coagulation Factors; D002712:Chlorides; D005290:Ferric Compounds; D015850:Interleukin-6; D052638:Particulate Matter; D004002:Clodronic Acid; D013917:Thrombin; C024555:ferric chloride