| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
University of Michigan Health System, Ann Arbor, MI 48109
CCR2 is required for monocyte recruitment in many inflammatory processes, as well as conferring Th1 lymphokine responses. Deep vein thrombosis (DVT) resolution represents a specific inflammatory response whereby the thrombus must be dissolved for restoration of blood flow. Using a stasis model of DVT in the mouse, we investigated the role of CCR2 on DVT resolution. Genetic deletion of CCR2 (CCR2–/–) was associated with larger thrombi at early and later time points, increased thrombus collagen, fewer thrombus monocytes (F4/80), and significantly impaired neovascularization. IL-2 and IFN-
were significantly reduced in early CCR2–/– thrombi, whereas MCP-1 was significantly increased, and Th2 lymphokines were unaffected. Supplementation of CCR2–/– mice with IFN- normalized early thrombus resolution without increasing monocyte influx. Neither Ab depletion of IFN- nor genetic deletion of IFN- impaired early DVT resolution. Early fibrinolysis was not impaired in CCR2–/– mice, but a significant reduction in both matrix metalloproteinase (MMP)-2 and MMP-9 activity was observed. However, only MMP-9 activity was restored with administration of IFN-. We conclude that an early CCR2-dependent Th1 lymphokine response predominates in normal DVT resolution, mediates this in part by MMP-9 activation, but is not solely dependent on IFN-.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grant 675317 (to P.K.H.).
2 Presented in part at the 66th Annual Meeting of the Society of University Surgeons, February 11, 2005, Nashville, TN.
3 Address correspondence and reprint requests to Dr. Peter K. Henke, University of Michigan Health System, 1500 East Medical Center Drive, 2210 Taubman Health Care Center, Ann Arbor, MI 48109-0329. E-mail address: henke{at}umich.edu
4 Abbreviations used in this paper: DVT, deep vein thrombosis; PMN, polymorphonuclear neutrophil; VEGF, vascular endothelial growth factor; bFGF, basic fibroblast growth factor; uPA, urokinase plasminogen activator; MMP, matrix metalloproteinase; WT, wild type; IVC, inferior vena cava; vWF, von Willebrand factor; hpf, high power field; PAI-1, plasminogen activator inhibitor-1.
This article has been cited by other articles:
|
|
 |
|
  M. J. Tracz, J. P. Juncos, J. P. Grande, A. J. Croatt, A. W. Ackerman, Z. S. Katusic, and K. A. Nath Induction of Heme Oxygenase-1 is a Beneficial Response in a Murine Model of Venous Thrombosis Am. J. Pathol., December 1, 2008; 173(6): 1882 - 1890. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. W. Wakefield, D. D. Myers, and P. K. Henke Mechanisms of Venous Thrombosis and Resolution Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 387 - 391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Westrick, M. E. Winn, and D. T. Eitzman Murine Models of Vascular Thrombosis Arterioscler Thromb Vasc Biol, October 1, 2007; 27(10): 2079 - 2093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Henke Commentary on "The Issue of Spontaneous Arteriovenous Fistulae after Superficial Thrombophlebitis, Endovenous Ablations, and Deep Vein Thrombosis: An Unusual but Predictable Finding" Perspectives in Vascular Surgery and Endovascular Therapy, September 1, 2006; 18(3): 251 - 252. [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
