Abstract
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-γ were significantly reduced in early CCR2-/- thrombi, whereas MCP-1 was significantly increased, and Th2 lymphokines were unaffected. Supplementation of CCR2-/- ice with IFN-γ normalized early thrombus resolution without increasing monocyte influx. Neither Ab depletion of IFN-γ nor genetic deletion of IFN-γ 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-γ. 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-γ.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3388-3397 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 177 |
| Issue number | 5 |
| State | Published - Sep 1 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
Targeted deletion of CCR2 impairs deep vein thombosis resolution in a mouse model. / Henke, Peter K.; Pearce, Charles G.; Moaveni, Daria; Moore, Andrea J.; Lynch, Erin M.; Longo, Christopher; Varma, Manu; Dewyer, Nicholas A.; Deatrick, K. Barry; Upchurch, Gilbert R.; Wakefield, Thomas W.; Hogaboam, Cory; Kunkel, Steven L.
In: Journal of Immunology, Vol. 177, No. 5, 01.09.2006, p. 3388-3397.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Targeted deletion of CCR2 impairs deep vein thombosis resolution in a mouse model
AU - Henke, Peter K.
AU - Pearce, Charles G.
AU - Moaveni, Daria
AU - Moore, Andrea J.
AU - Lynch, Erin M.
AU - Longo, Christopher
AU - Varma, Manu
AU - Dewyer, Nicholas A.
AU - Deatrick, K. Barry
AU - Upchurch, Gilbert R.
AU - Wakefield, Thomas W.
AU - Hogaboam, Cory
AU - Kunkel, Steven L.
PY - 2006/9/1
Y1 - 2006/9/1
N2 - 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-γ were significantly reduced in early CCR2-/- thrombi, whereas MCP-1 was significantly increased, and Th2 lymphokines were unaffected. Supplementation of CCR2-/- ice with IFN-γ normalized early thrombus resolution without increasing monocyte influx. Neither Ab depletion of IFN-γ nor genetic deletion of IFN-γ 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-γ. 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-γ.
AB - 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-γ were significantly reduced in early CCR2-/- thrombi, whereas MCP-1 was significantly increased, and Th2 lymphokines were unaffected. Supplementation of CCR2-/- ice with IFN-γ normalized early thrombus resolution without increasing monocyte influx. Neither Ab depletion of IFN-γ nor genetic deletion of IFN-γ 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-γ. 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-γ.
UR - http://www.scopus.com/inward/record.url?scp=33747780746&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33747780746&partnerID=8YFLogxK
M3 - Article
C2 - 16920980
AN - SCOPUS:33747780746
VL - 177
SP - 3388
EP - 3397
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 5
ER -