P-Selectin and TNF Inhibition Reduce Venous Thrombosis Inflammation

Wakefield, Thomas W.; Strieter, Robert M.; Downing, L.; Kadell, Amy M.; Wilke, Carol A.; Burdick, Marie D.; Wrobleski, Shirley K.; Phillips, M. L.; Paulson, James C.; Anderson, Donald C.; Greenfield, Lazar J.

doi:10.1006/jsre.1996.0301

Cited by 65 publications

(43 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although studies have demonstrated that immunoneutralization of P-selectin reduces the vein wall cytokine elevation, edema, and thrombosis several days after stasis, 13,15 relatively little is known regarding the role of cell adhesion molecules in mediating leukocyte adhesion and transmigration during the pathogenesis of DVT. In the baboon, Downing et al 15 demonstrated that P-selectin mAbs were ineffective at reducing leukocyte accumulation in the vein wall 48 hours after occlusion.…”

Section: Discussionmentioning

confidence: 99%

P-Selectin–Dependent Inhibition of Thrombosis During Venous Stasis

Eppihimer¹,

Schaub²

2000

ATVB

View full text Add to dashboard Cite

Abstract-Leukocyte adhesion, transendothelial migration, and stasis are important components in the pathogenesis of deep vein thrombosis. Anesthetized cats were treated with saline, a recombinant soluble form of P-selectin glycoprotein ligand-1 (rPSGL-Ig), or an E-and L-selectin antibody (EL-246) before exposure and occlusion of a jugular vein. After 2 or 6 hours of occlusion, jugular veins were perfused with buffer, fixed, and prepared for scanning electron microscopy. In cats receiving saline, 2 and 6 hours of occlusion produced moderate levels of leukocyte and platelet adhesion and endothelial cell injury. Treatment of cats with rPSGL-Ig or EL-246 had no apparent effect on the magnitude of cell adhesion and endothelial cell injury compared with no treatment. After 6 hours of occlusion, the presence of a mural thrombus in untreated veins was observed and confirmed by scanning electron microscopy. Pretreatment of cats with rPSGL-Ig completely (4.0 mg/kg) or partially (1.0 mg/kg) prevented the occurrence of thrombi in the jugular veins. The reduction in thrombosis by rPSGL-Ig treatment after 6 hours of venous stasis, in the absence of any effect on leukocyte-mediated endothelial cell injury, suggests an antithrombotic mechanism of action for this protein.

show abstract

Section: Discussionmentioning

confidence: 99%

P-Selectin–Dependent Inhibition of Thrombosis During Venous Stasis

Eppihimer¹,

Schaub²

2000

ATVB

View full text Add to dashboard Cite

show abstract

“…The CAMs P-and E-selectin and ICAM-1 are critical for leukocyte tethering, firm adhesion, and emigration, respectively. Leukocyte emigration into the vein wall allows the release of cytotoxic inflammatory intermediates that cause vein damage (4,6,8,9,(13)(14)(15). Prior work in our laboratory has clarified that TNF-␣ and P-selectin are central mediators of post-thrombotic vein wall inflammation and direct the magnitude of thrombus production (6,(13)(14)(15).…”

Section: Eep Vein Thrombosis (Dvt)mentioning

confidence: 99%

“…This rat model is a modification of a well-characterized method for reproducible stasis induced venous thrombosis (3,5,6,13,24). In brief, male Sprague Dawley rats, weighing 250 -300 g, were anesthetized with an inhalation mixture of isoflurane (1-2%) and oxygen (100%) during the procedure.…”

Section: Animal Model Transfection and Tissue Analysismentioning

confidence: 99%

“…Leukocyte infiltration into the vein wall was assessed as previously described (3,5,6,13). In brief, leukocyte morphometric analysis was performed in a blinded fashion on hematoxylin-and eosin-stained sections.…”

Section: Histopathologic Analysis and Immunohistochemical Stainingmentioning

confidence: 99%

“…All other mediator analysis was performed on single rat vein tissue samples. Tissue homogenate ELISAs for the aforementioned mediators were quantified using a double-ligand technique as previously described (5,6,13). In brief, flat-bottom 96-well microtiter plates (Immuno-Plate I 96-F, Nunc, Naperville, IL) were coated with 50 l/well (1 ng/ml) of the specific rabbit anti-cytokine Ab in coating buffer (0.6 mol/L NaCl, 0.26 mol/L H 3 PO 4 , and 0.08 N NaOH, pH 9.6) for 16 -24 h at 0°C.…”

Section: Cytokine/coagulation Factor/cam Analysismentioning

confidence: 99%

See 2 more Smart Citations

Viral IL-10 Gene Transfer Decreases Inflammation and Cell Adhesion Molecule Expression in a Rat Model of Venous Thrombosis

Henke

DeBrunye²,

Strieter

et al. 2000

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Post-thrombotic inflammation probably contributes to chronic venous insufficiency, and little effective treatment exists. IL-10 is an anti-inflammatory cytokine that previously has been shown to decrease perithrombotic inflammation and thrombosis. We investigated in a rat model whether local expression of viral IL-10 (vIL-10) in a segment of vein that undergoes thrombosis would confer an anti-inflammatory effect and how this effect might be mediated. Rats underwent inferior vena cava isolation, cannulation, and instillation of saline or adenovirus encoding either β-galactosidase or vIL-10. Two days after transfection, thrombosis was induced, 2 days after this the rats underwent gadolinium (Gd)-enhanced magnetic resonance venography exam, and the vein segments were harvested. Tissue transfection was confirmed by either RT-PCR of vIL-10 or positive 5-bromo-4-chloro-3-indolyl β-d-galactopyranoside (X-Gal) staining. vIL-10 significantly decreased both leukocyte vein wall extravasation and area of Gd enhancement compared with those in controls, suggesting decreased inflammation. Immunohistochemistry demonstrated decreased endothelial border staining of P- and E-selectin, while ELISA of vein tissue homogenates revealed significantly decreased P- and E-selectin and ICAM-1 levels in the vIL-10 group compared with those in controls. Importantly, native cellular IL-10 was not significantly different between the groups. However, neither clot weight nor coagulation indexes, including tissue factor activity, tissue factor Ag, or von Willebrand factor levels, were significantly affected by local vIL-10 expression. These data suggest that local transfection of vIL-10 decreases venous thrombosis-associated inflammation and cell adhesion molecule expression, but does not directly affect local procoagulant activity.

show abstract