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

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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.

Annotation

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