Activation of cultured vascular endothelial cells by antiphospholipid antibodies.

Simantov, Ronit; LaSala, Johanna M.; Lo, S. K.; Gharavi, Azzudin E.; Sammaritano, Lisa R.; Salmon, Jane E.; Silverstein, Roy L.

doi:10.1172/jci118276

Cited by 400 publications

(278 citation statements)

References 27 publications

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“…Several studies have demonstrated that aPL activate ECs in vitro, suggesting a mechanism by which these antibodies exert procoagulant properties (15,49,50). Utilizing a mouse model, our group has previously demonstrated that aPL antibodies increase leukocyte adhesion to ECs of cremasteric muscle postcapillary venules, suggesting that these antibodies induce activation of ECs in vivo and that these effects correlate with enhanced thrombus formation (37).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model

Ferrara¹,

Liu²,

Espinola³

et al. 2003

Arthritis & Rheumatism

138

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Methods. Two groups of CD-1 male mice, each comprising ϳ18 mice, were fed either normal saline solution or 15 mg/kg fluvastatin for 15 days. Each of the 2 groups was further subdivided to receive either purified IgG from patients with the antiphospholipid syndrome (IgG-APS) or normal IgG from healthy subjects. Analysis of thrombus dynamics was performed in treated and control mice, using a standardized thrombogenic injury procedure, and the area (size) of the thrombus was measured. Adhesion of leukocytes to ECs was analyzed with a microcirculation model of exposed cremaster muscle. Baseline and posttreatment soluble intercellular adhesion molecule 1 (sICAM-1) levels were determined by enzyme-linked immunosorbent assay.Results. IgG-APS mice treated with fluvastatin showed significantly smaller thrombi, a reduced number of adherent leukocytes, and decreased levels of sICAM-1 compared with IgG-APS animals treated with placebo.Conclusion. These findings indicate that fluvastatin significantly diminishes aPL-mediated thrombosis and EC activation in vivo. These results may have important implications for the design of new treatment strategies aimed at preventing recurrent thrombosis in patients with APS.

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Section: Discussionmentioning

confidence: 99%

Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model

Ferrara¹,

Liu²,

Espinola³

et al. 2003

Arthritis & Rheumatism

138

View full text Add to dashboard Cite

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“…Some aPL bind to endothelial cells, suggesting that aPL may interact with endothelial cells and thus promote thrombosis (68,69). APTs can bind to immobilized PS in the presence of calcium and prothrombin (28,29), and a LAC IgG preparation can enhance the binding of prothrombin to endothelial cells and increase thrombin generation on these cells (45), suggesting that APT may concentrate prothrombin on cell surface phospholipids and thus lead to a hypercoagulable state.…”

Section: Pathogenic Role Of Aptsmentioning

confidence: 99%

Specificities, properties, and clinical significance of antiprothrombin antibodies

Amengual

Atsumi

Koike

2003

Arthritis & Rheumatism

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“…The nature of the cell surface "receptor" for P,GPI is not known. Antibody binding to &GPI on the endothelial cell surface induced the expression of the adhesion molecules E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 (44,89), and enhanced monocyte adhesion to cultured endothelial cells (89).…”

Section: Mechanisms Of Thrombosismentioning

confidence: 99%

Immunology of the antiphospholipid antibody syndrome

Roubey

1996

Arthritis & Rheumatism

286

170

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Like the femme fatale in The Beatles' Rocky Raccoon, antiphospholipid antibodies (aPL) and the syndrome with which they are associated (thrombosis, recurrent fetal deaths, thrombocytopenia) have attracted considerable attention despite a serious nomenclature problem. Along with increasing experience in the optimal management of patients with the aPL syndrome and growing evidence that autoantibodies may play a direct pathophysiologic role, research over the past several years demonstrates that a large proportion of "antiphospholipid" autoantibodies do not, in fact, recognize phospholipids. These new data indicate that the antigenic targets of antibodies detected in conventional anticardiolipin and lupus anticoagulant assays are phospholipid-binding plasma proteins, most notably, &-glycoprotein I (&GPI) and prothrombin or complexes of these proteins with phospholipids. Further, autoantibodies to other phospholipid-binding plasma proteins and certain molecules expressed on vascular endothelium may also be associated with the antiphospholipid antibody syndrome (APS) although they are not detectable in standard aPL assays.This review summarizes recent information on the specificities of autoantibodies associated with APS and discusses the insights these data offer into the potential role of autoantibodies in the syndrome's pathophysiology. Antigenic specificities of aPL: historical perspective Current concepts of aPL date to the early part of this century and the development of nontreponemal serologic tests for syphilis (STS). In the early 1940s, Mary Pangborn identified the antigenic component of the tissue extracts used in these tests as a novel anionic phospholipid, which she named cardiolipin (1). As a result of widespread population screening for syphilis, in the 1950s it was observed that individuals with chronically false-positive STS results, when followed up for many years, often developed systemic lupus erythematosus (SLE) (2). False-positive STS results were also noted to be present in early reports of SLE patients with acquired inhibitors of in vitro phospholipid-dependent coagulation tests, in particular, the activation of prothrombin (3). Laurel1 and Nilsson investigated this association and suggested that the anticoagulant effect and the positive reactions with phospholipid antigen were ascribable to the same causal factor (4). Additional support for the hypothesis that these acquired coagulation inhibitors were directed against phospholipid came from studies demonstrating that the anticoagulant effect was enhanced when the phospholipid in the test system was diluted (5).In contrast, a number of key features of the inhibitors, subsequently termed lupus anticoagulants (6), were not compatible with phospholipid specificity and suggested an important role of plasma proteins. First, certain lupus anticoagulants were species specific, for example, they prolonged coagulation reactions of human plasma but not bovine plasma (7). Second, certain lupus anticoagulants did not inhibit phospholipid-dependent reacti...

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Activation of cultured vascular endothelial cells by antiphospholipid antibodies.

Cited by 400 publications

References 27 publications

Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model

Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model

Specificities, properties, and clinical significance of antiprothrombin antibodies

Immunology of the antiphospholipid antibody syndrome

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