RGD Reference Report - Targeted deletion of CCR2 impairs deep vein thombosis resolution in a mouse model. - Rat Genome Database

Send us a Message

Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Targeted deletion of CCR2 impairs deep vein thombosis resolution in a mouse model.

Authors: Henke, PK  Pearce, CG  Moaveni, DM  Moore, AJ  Lynch, EM  Longo, C  Varma, M  Dewyer, NA  Deatrick, KB  Upchurch GR, JR  Wakefield, TW  Hogaboam, C  Kunkel, SL 
Citation: Henke PK, etal., J Immunol. 2006 Sep 1;177(5):3388-97.
RGD ID: 1582648
Pubmed: (View Article at PubMed) PMID:16920980

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-gamma were significantly reduced in early CCR2-/- thrombi, whereas MCP-1 was significantly increased, and Th2 lymphokines were unaffected. Supplementation of CCR2-/- mice with IFN-gamma normalized early thrombus resolution without increasing monocyte influx. Neither Ab depletion of IFN-gamma nor genetic deletion of IFN-gamma 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-gamma. 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-gamma.


Disease Annotations    
Venous Thrombosis  (IDA,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
MMP9  (matrix metallopeptidase 9)

Additional Information