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

Seshan, Surya V.; Franzke, Claus Werner; Redecha, Patricia; Monestier, Marc; Mackman, Nigel; Girardi, Guillermina

doi:10.1182/blood-2009-01-199117

Cited by 72 publications

(54 citation statements)

References 36 publications

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“…The mechanisms by which aPL induce thrombosis in APS have not been fully elucidated, but likely include activation of complement, endothelial cells, monocytes, and platelets (40,41). A more widespread activation of endothelial cells and complement may be more prominent in CAPS.…”

Section: Discussionmentioning

confidence: 99%

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A 26‐year‐old white man with a systemic lupus erythematosus flare and acute multiorgan ischemia: Vasculitis or thrombosis?

Cherian¹,

Duculan²,

Amigues³

et al. 2011

Arthritis Care & Research

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A 26-year-old white man with a systemic lupus erythematosus (SLE) flare and acute multiorgan ischemia. History of the present illnessThe patient was in his usual state of health until 2 months before admission, when he developed pain and stiffness in his right shoulder, neck, and back after playing softball. His symptoms progressively worsened despite manipulation by a chiropractor, and he developed new pain in his soles. This was diagnosed as plantar fasciitis and he was given a topical steroid injection and a short course of methylprednisolone. This treatment improved his pain, but at its completion, he developed disabling diffuse arthralgias in his shoulders, elbows, knees, and feet, along with fevers, anorexia, and weight loss. Worsening symptoms prompted hospitalization in another institution 3 weeks before admission, where he was febrile up to 103°F and hypertensive (144/100 mm Hg). An extensive evaluation revealed elevated inflammatory markers, including erythrocyte sedimentation rate (ESR; 102 mm/hour), C-reactive protein level (56 mg/liter), positive antinuclear antibodies (ANAs; Ͼ1:640), strongly positive anti-doublestranded DNA (anti-dsDNA) titers, low levels of C4 (9 mg/dl, normal range 16 -38), prolonged prothrombin time (16.2 seconds, normal range 10 -13), prolonged activated partial thromboplastin time (60 seconds, normal range 27-38), and positive lupus anticoagulant (LAC) by dilute Russell's viper venom time. His urine analysis showed proteinuria (0.440 gm protein/gm creatinine), hematuria (11-25 red blood cells [RBCs]/high-power field [hpf]), and pyuria (3-10 white blood cells [WBCs]/hpf). Antibodies to Sm/RNP, Ro/SSA, and La/SSB; anticardiolipin antibodies; antineutrophil cytoplasmic antibodies (ANCAs); and anticyclic citrullinated peptide antibodies were negative, and creatine phosphokinase was normal. An infectious disease evaluation was performed and was negative for all pathogens, including Lyme disease, human immunodeficiency virus, and viral hepatitis. Renal ultrasound and Doppler were performed and were negative for renal pathology and venous thrombosis. He was placed on prednisone 10 mg orally twice daily, losartan 50 mg daily, and aspirin 81 mg daily, and his fevers resolved with some improvement in joint pains. Two weeks before admission, he was evaluated by a rheumatologist who discontinued aspirin in anticipation of a kidney biopsy to rule out lupus nephritis. Laboratory evaluation again revealed persistent proteinuria (2ϩ), hematuria (10 -20 RBCs/hpf), C4 hypocomplementemia (C3 111 mg/dl, C4 9 mg/dl), and strongly positive anti-dsDNA. The patient could not tolerate tapering of prednisone to 15 mg and he stayed at 17.5 mg daily.He presented to our clinic 3 days before admission and his scheduled kidney biopsy. Over the course of the previous week he had developed a few small tender erythematous skin lesions and some skin excoriation on his fingers and palms. He also experienced numbness of his fingertips and bilateral soles for 2 or 3 days. Weight loss of 30 -33 pounds over the cou...

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Section: Discussionmentioning

confidence: 99%

“…Tissue factor may also be expressed in circulating detached endothelial cells or activated by cytokines in intact endothelium. Interestingly, in a mouse model of TMA induced by aPL, genetic reduction of tissue factor levels prevented glomerular injury (41).…”

Section: Discussionmentioning

confidence: 99%

A 26‐year‐old white man with a systemic lupus erythematosus flare and acute multiorgan ischemia: Vasculitis or thrombosis?

Cherian¹,

Duculan²,

Amigues³

et al. 2011

Arthritis Care & Research

View full text Add to dashboard Cite

show abstract

“…injection of clodronate liposomes (16,17). This method depletes phagocytic monocytes, with effective depletion of bone marrow and circulating monocytes (thus effectively suppressing monocyte trafficking into inflammatory sites) and more variable depletion of tissue macrophages.…”

Section: Gr1mentioning

confidence: 99%

Proliferative lesions and metalloproteinase activity in murine lupus nephritis mediated by type I interferons and macrophages

Triantafyllopoulou

Franzke

Seshan³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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136

112

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Glomerulonephritis is a major cause of morbidity in patients with systemic lupus erythematosus. Although substantial progress has been made in the identification of pathogenic triggers that result in autoantibody production, little is known about the pathogenesis of aggressive proliferative processes that lead directly to irreversible glomerular damage and compromise of renal function. In this study, we describe a model of polyinosinic: polycytidylic acid-accelerated lupus nephritis in NZB/W mice that is characterized by severe glomerular proliferative lesions with de novo crescent formation, findings that are linked with decreased survival and adverse outcomes in lupus. Proliferative glomerulonephritis was associated with infiltrating kidney macrophages and renal expression of IFNinducible genes, matrix metalloproteinases (MMPs), and growth factors. Crescent formation and renal MMP and growth factor expression were dependent on renal macrophages that expressed Il10, MMPs, osteopontin, and growth factors, including Pdgfc and Hbegf. Infiltrating macrophages and renal MMP expression were induced by type I IFN. These findings reveal a role for type I IFNs and alternatively activated macrophages in aggressive proliferative lesions of lupus nephritis.alternative macrophages | kidney disease | polyinosinic: polycytidylic acid | systemic lupus erythematosus | tissue repair

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“…42,43 Even though no TF-dependent procoagulant activity has been detected in whole blood stimulated with different agents, 44 there is increasing evidence that neutrophils may be able to express TF under specific inflam- matory conditions. [45][46][47] For instance, the complement factor C5a induces TF expression in neutrophils both in vitro and in vivo 47,48 ; thus pointing to a role of TF in the antiphospholipid-syndrome which is going on with an activated complement system. In addition to the de novo synthesis of TF in neutrophils, granulocytes may take up TF via TF-positive microparticles (MPs).…”

Section: Granulocytesmentioning

confidence: 99%

Tissue Factor and Cardiovascular Disease: Quo Vadis?

Berndt

Tanner

Lüscher

2010

Circ J

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The coagulation cascade represents a system of proteases responsible to maintain vascular integrity and to induce rapid clot formation after vessel injury. Tissue factor (TF), the key initiator of the coagulation cascade, binds to factor VIIa and thereby activates factor IX and factor X, resulting in thrombus formation. Different stimuli enhance TF gene expression in endothelial and vascular smooth muscle cells. In addition to these vascular cells, TF has recently been detected in the bloodstream in circulating cells such as leukocytes and platelets, as a component of microparticles, and as a soluble, alternatively spliced form of TF. Various cardiovascular risk factors like hypertension, diabetes, and dyslipidemia, increase levels of TF. In line with this observation, enhanced vascular TF expression occurs during atherogenesis, particularly in patients with acute coronary syndromes. (Circ J 2010; 74: 3 - 12)

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

Cited by 72 publications

References 36 publications

A 26‐year‐old white man with a systemic lupus erythematosus flare and acute multiorgan ischemia: Vasculitis or thrombosis?

A 26‐year‐old white man with a systemic lupus erythematosus flare and acute multiorgan ischemia: Vasculitis or thrombosis?

Proliferative lesions and metalloproteinase activity in murine lupus nephritis mediated by type I interferons and macrophages

Tissue Factor and Cardiovascular Disease: Quo Vadis?

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