A Complement-Dependent Model of Thrombotic Thrombocytopenic Purpura Induced by Antibodies Reactive with Endothelial Cells

Ren, Guanghui; Hack, Bradley K.; Minto, Andrew W.; Cunningham, Patrick N.; Alexander, Jessy J.; Haas, Mark; Quigg, Richard J.

doi:10.1006/clim.2002.5168

Cited by 21 publications

(11 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additional studies using this model also suggested a role for C5b-9-mediated endothelial cell apoptosis and showed protective effects of VEGF. A further rat model of TMA with renal disease was developed by Ren et al [[8]], using a complement-fixing antibody to endothelial cells. EC injury was prevented by complement depletion and worsened by blockade of Crry.…”

Section: Animal Models Of Thrombotic Microangiopathies (Tables 1 2)mentioning

confidence: 99%

Pathogenesis of Thrombotic Microangiopathy: Insights from Animal Models

Richards

Kavanagh

2009

Nephron Exp Nephrol

View full text Add to dashboard Cite

Animal models are important experimental tools for investigating the molecular mechanisms, environmental and genetic susceptibilities underlying the development of thrombotic microangiopathies. Large mammal, small animal models, knockout, transgenic and conditional knockout mouse models are available to investigate haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura and vascular endothelial growth factor-associated thrombotic microangiopathy. These models have shown that it is possible to model the human conditions. However, differences in human and rodent physiology mean that caution is required when interpreting the findings. These models offer realistic prospects for identifying and testing novel therapeutic strategies in a range of thrombotic microangiopathies prior to human trials.

show abstract

Section: Animal Models Of Thrombotic Microangiopathies (Tables 1 2)mentioning

confidence: 99%

Pathogenesis of Thrombotic Microangiopathy: Insights from Animal Models

Richards

Kavanagh

2009

Nephron Exp Nephrol

View full text Add to dashboard Cite

show abstract

“…In hyperacute xenograft rejection, there is endothelial cell activation and generation of a procoagulant mileu, which results in thrombosis, platelet consumption, hemorrhage, and infarction (65), while in acute humoral rejection of the allograft there is neutrophil infiltration, arterial fibrinoid necrosis, and acute tubular injury (66). There are experimental rodent models to substantiate that Ab reactivity with endothelium can lead to C-dependent endothelial cell alterations similar to those described in transplant rejection (67)(68)(69). In addition, C inhibition with soluble rCR1 has been shown to be beneficial in allograft rejection in the rat (70).…”

Section: Transplantationmentioning

confidence: 99%

Complement and the Kidney

Quigg

2003

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

“…[7][8][9][10] Most of these models require uninephrectomy and direct intraarterial injection of antibodies. [7][8][9] Another model involves gammaray irradiation of the kidneys; however, signs of renal impairment in this model are not observed until 40 weeks of treatment. 10 We developed a mouse model of TMA that has the advantage of using smaller amounts of antibodies and fast development of disease.…”

Section: Introductionmentioning

confidence: 99%

Role of tissue factor in a mouse model of thrombotic microangiopathy induced by antiphospholipid antibodies

Seshan¹,

Franzke

Redecha

et al. 2009

Blood

View full text Add to dashboard Cite

Using different mouse monoclonal and human antiphospholipid (aPL) antibodies, we developed a new animal model of renal injury that shares many features with thrombotic microangiopathy (TMA). We found that more than 1 mechanism/signaling pathway is involved in glomerular injury induced by aPL antibodies in this model. Both complement-dependent and complementindependent pathways were identified that lead to glomerular endothelial cell damage and renal function impairment. We also found that C5a-C5aR interaction is a crucial step for the activation of the coagulation cascade and glomerular injury induced by complement-activating antibodies. In addition, our studies demonstrated complementindependent mechanisms in which reactivity with ␤ 2 glycoprotein I (␤2GPI) plays an important role in aPL-induced glomerular damage and renal failure. Independently of the mechanism responsible for aPL-induced TMA, mice that express low levels of tissue factor (TF) were protected from glomerular

show abstract

A Complement-Dependent Model of Thrombotic Thrombocytopenic Purpura Induced by Antibodies Reactive with Endothelial Cells

Cited by 21 publications

References 48 publications

Pathogenesis of Thrombotic Microangiopathy: Insights from Animal Models

Pathogenesis of Thrombotic Microangiopathy: Insights from Animal Models

Complement and the Kidney

Role of tissue factor in a mouse model of thrombotic microangiopathy induced by antiphospholipid antibodies

Contact Info

Product

Resources

About