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

被引：97

作者：

Henke, Peter K. ^{[1
]}

Pearce, Charles G. ^{[1
]}

Moaveni, Daria M. ^{[1
]}

Moore, Andrea J. ^{[1
]}

Lynch, Erin M. ^{[1
]}

Longo, Christopher ^{[1
]}

Varma, Manu ^{[1
]}

Dewyer, Nicholas A. ^{[1
]}

Deatrick, K. Barry ^{[1
]}

Upchurch, Gilbert R., Jr. ^{[1
]}

Wakefield, Thomas W. ^{[1
]}

Hogaboam, Cory ^{[1
]}

Kunkel, Steven L. ^{[1
]}

机构：

[1] Univ Michigan, Hlth Syst, Ann Arbor, MI 48109 USA

来源：

JOURNAL OF IMMUNOLOGY | 2006年 / 177卷 / 05期

关键词：

D O I：

10.4049/jimmunol.177.5.3388

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：3388 / 3397

页数：10

共 52 条

[1] CYTOKINES AND GROWTH-FACTORS POSITIVELY AND NEGATIVELY REGULATE INTERSTITIAL COLLAGEN GENE-EXPRESSION IN HUMAN VASCULAR SMOOTH-MUSCLE CELLS [J].