Interleukin-8 Administration Enhances Venous Thrombosis Resolution in a Rat Model

Henke, Peter K.; Wakefield, Thomas W.; Kadell, Amy M.; Linn, Marisa J.; Varma, Manu R.; Sarkar, Minaski; Hawley, Angela E.; Fowlkes, J. Brian; Strieter, Robert M.

doi:10.1006/jsre.2001.6122

Cited by 97 publications

(133 citation statements)

References 26 publications

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“…Restoration of blood flow in a thrombosed vein also involves neovascularization with functional flow channels, thrombus retraction, and fibrinolysis (7,18,19). Histological studies have confirmed the appearance of intrathrombus clefts and neovascular channels that evolve mostly within the first 4 wk (7,18,20).…”

Section: Eep Vein Thrombosis (Dvt)mentioning

confidence: 95%

“…Histological studies have confirmed the appearance of intrathrombus clefts and neovascular channels that evolve mostly within the first 4 wk (7,18,20). Pleotropic angiogenic growth factors released by polymorphonuclear neutrophils (PMNs) and monocytes are known to be present in the resolving thrombus and include vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) (21)(22)(23).…”

Section: Eep Vein Thrombosis (Dvt)mentioning

confidence: 95%

“…Although four main chemokine families exist, the ones most relevant to DVT resolution are the cysteine-cysteine (CC) and cysteine-X-cysteine (CXC) chemokine types. For example, both CXC and CC chemokines are present within a resolving thrombus (4), and exogenous administration of IL-8 (CXC chemokine) and MCP-1 (a CC chemokine) have been shown to accelerate thrombus resolution in experimental models (7,8). Many pathophysiological processes involve CCR2 signaling, including peritoneal and pulmonary inflammation, and atherogenesis (9 -11).…”

Section: Eep Vein Thrombosis (Dvt)mentioning

confidence: 99%

“…The rodent model of stasis-induced DVT has been well described (4,5,7,30) and used B6/129 (wild-type (WT) controls, F2 hybrids; The Jackson Laboraory) and B6/129 CCR2 Ϫ/Ϫ mice (10) weighing 20 -30 g, between 4 and 6 wk old. The mice underwent general inhalational anesthesia and, via a laparotomy, the inferior vena cava (IVC) was ligated with a 6-0 polypropylene suture.…”

Section: Mouse Modelmentioning

confidence: 99%

“…Immunohistochemical staining was performed on the paraffin-embedded tissue sections (10 m) as described (7,18,19,34). Anti-PMN (1/1000; Accurate Chemical and Scientific), anti-F4/80 (1/100; Serotec), anti-CCR2 (1/100; Santa Cruz Biotechnology), anti-uPA (1/250; Santa Cruz Biotechnology), and anti-von Willebrand factor (vWF; 1/100; Serotec) were used.…”

Section: Histological Analysis/immunohistochemical Staining/neovasculmentioning

confidence: 99%

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Targeted Deletion of CCR2 Impairs Deep Vein Thombosis Resolution in a Mouse Model

Henke

Pearce

Moaveni

et al. 2006

The Journal of Immunology

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109

177

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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−/− mice 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.

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Section: Eep Vein Thrombosis (Dvt)mentioning

confidence: 95%

Section: Eep Vein Thrombosis (Dvt)mentioning

confidence: 95%

Section: Eep Vein Thrombosis (Dvt)mentioning

confidence: 99%

Section: Mouse Modelmentioning

confidence: 99%

Section: Histological Analysis/immunohistochemical Staining/neovasculmentioning

confidence: 99%

See 3 more Smart Citations

Targeted Deletion of CCR2 Impairs Deep Vein Thombosis Resolution in a Mouse Model

Henke

Pearce

Moaveni

et al. 2006

The Journal of Immunology

Self Cite

109

177

View full text Add to dashboard Cite

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Methods and Applications of Anticoagulation Assays

Zhao

2009

Pharmaceutical Bioassays

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Tissue factor upregulation drives a thrombosis–inflammation circuit in relation to cardiovascular complications

Chu

2006

Cell Biochem. Funct.

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The extrinsic coagulation is recognized as an 'inducible' signalling cascade resulting from tissue factor (TF) upregulation by exposure to clotting zymogen FVII upon inflammation or tissue injury. Following the substantial initiation, an array of proteolytic activation generates mediating signals (active serine proteases: FVIIa, FXa and FIIa) that lead to hypercoagulation with fibrin overproduction manifesting thrombosis. In addition, TF upregulation plays a central role in driving a thrombosis-inflammation circuit. Coagulant mediators (FVIIa, FXa and FIIa) and endproduct (fibrin) are proinflammatory, eliciting tissue necrosis factor, interleukins, adhesion molecules and many other intracellular signals in different cell types. Such resulting inflammation could ensure 'fibrin' thrombosis via feedback upregulation of TF. Alternatively, the resulting inflammation triggers platelet/leukocyte/polymononuclear cell activation thus contributing to 'cellular' thrombosis. TF is very vulnerable to upregulation resulting in hypercoagulability and subsequent thrombosis and inflammation, either of which presents cardiovascular risks. The prevention and intervention of TF hypercoagulability are of importance in cardioprotection. Blockade of inflammation reception and its intracellular signalling prevents TF expression from upregulation. Natural (activated protein C, tissue factor pathway inhibitor, or antithrombin III) or pharmacological anticoagulants readily offset the extrinsic hypercoagulation mainly through FVIIa, FXa or FIIa inhibition. Therefore, anticoagulants turn off the thrombosis-inflammation circuit, offering not only antithrombotic but anti-inflammatory significance in the prevention of cardiovascular complications.

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Interleukin-8 Administration Enhances Venous Thrombosis Resolution in a Rat Model

Cited by 97 publications

References 26 publications

Targeted Deletion of CCR2 Impairs Deep Vein Thombosis Resolution in a Mouse Model

Targeted Deletion of CCR2 Impairs Deep Vein Thombosis Resolution in a Mouse Model

Methods and Applications of Anticoagulation Assays

Tissue factor upregulation drives a thrombosis–inflammation circuit in relation to cardiovascular complications

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