Inhibition of Prothrombinase by Human Secretory Phospholipase A2 Involves Binding to Factor Xa

Mounier, Carine; Hackeng, Tilman M.; Schaeffer, Francis; Faure, Grazyna; Bon, Cassian; Griffin, John H.

doi:10.1074/jbc.273.37.23764

Cited by 50 publications

(45 citation statements)

References 52 publications

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“…19). Affinities determined by ITC were lower than by kinetic SPR, as often observed (20), because of the smaller entropy change upon binding a surface-immobilized protein in SPR compared with free-protein binding in solution in ITC (21). To our knowledge, these affinities are among the highest obtained with a scaffold protein without an affinity maturation step (ref.…”

Section: Discussionmentioning

confidence: 75%

Remodeling a DNA-binding protein as a specific in vivo inhibitor of bacterial secretin PulD

Mouratou

Schaeffer

Guilvout

et al. 2007

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

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116

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We engineered a class of proteins that binds selected polypeptides with high specificity and affinity. Use of the protein scaffold of Sac7d, belonging to a protein family that binds various ligands, overcomes limitations inherent in the use of antibodies as intracellular inhibitors: it lacks disulfide bridges, is small and stable, and can be produced in large amounts. An in vitro combinatorial/ selection approach generated specific, high-affinity (up to 140 pM) binders against bacterial outer membrane secretin PulD. When exported to the Escherichia coli periplasm, they inhibited PulD oligomerization, thereby blocking the type II secretion pathway of which PulD is part. Thus, high-affinity inhibitors of protein function can be derived from Sac7d and can be exported to, and function in, a cell compartment other than that in which they are produced.calorimetry ͉ intrabody ͉ ribosome display ͉ Sac7d ͉ type II secretion system

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Section: Discussionmentioning

confidence: 75%

Remodeling a DNA-binding protein as a specific in vivo inhibitor of bacterial secretin PulD

Mouratou

Schaeffer

Guilvout

et al. 2007

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

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116

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“…Actually, this procoagulant nature was not anticipated, because previous studies showed that sPLA 2 , which is present in high concentrations in synovial fluid, inhibits coagulation (23,24,37,38). In line with such an effect of sPLA 2 was the lower exposure of PS by synovial microparticles, as reflected by the reduced binding of annexin V, most likely due to the breakdown of PS to lyso-PS.…”

Section: Discussionmentioning

confidence: 99%

Cell‐derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a factor VII–dependent mechanism

Berckmans¹,

Nieuwland²,

Tak³

et al. 2002

Arthritis & Rheumatism

180

169

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Objective. To determine the cellular origin of synovial microparticles, their procoagulant properties, and their relationship to local hypercoagulation.Methods. Microparticles in synovial fluid and plasma from patients with rheumatoid arthritis (RA; n ‫؍‬ 10) and patients with other forms of arthritis (non-RA; n ‫؍‬ 10) and in plasma from healthy subjects (n ‫؍‬ 20) were isolated by centrifugation. Microparticles were identified by flow cytometry. The ability of microparticles to support coagulation was determined in normal plasma. Concentrations of prothrombin fragment F 1؉2 (by enzyme-linked immunosorbent assay [ELISA]) and thrombin-antithrombin (TAT) complexes (by ELISA) were determined as estimates of the coagulation activation status in vivo.Results. Plasma from patients and healthy controls contained comparable numbers of microparticles, which originated from platelets and erythrocytes. Synovial microparticles from RA patients and non-RA patients originated mainly from monocytes and granulocytes; few originated from platelets and erythrocytes. Synovial microparticles bound less annexin V (which binds to negatively charged phospholipids) than did plasma microparticles, exposed tissue factor, and supported thrombin generation via factor VII. F 1؉2 (median 66 nM) and TAT complex (median 710 g/liter) concentrations were elevated in synovial fluid compared with plasma from the patients (1.6 nM and 7.0 g/liter, respectively) as well as the controls (1.0 nM and 2.9 g/liter, respectively). Conclusion. Synovial fluid contains high numbers of microparticles derived from leukocytes that are strongly coagulant via the factor VII-dependent pathway. We propose that these microparticles contribute to the local hypercoagulation and fibrin deposition in inflamed joints of patients with RA and other arthritic disorders.

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“…14 Venom and mammalian sPLA 2 also bind to a number of cell soluble proteins, such as pentraxins, 15 reticulocalbins, 16 calmodulin, 17 heparin, and to the serum coagulation factor Xa. 18 Several mammalian sPLA 2 such as group II and V enzymes also bind to heparan sulfate proteoglycans (HSPGs) like glypican-1 19 and decorin. 20 hGIIA is found in high concentrations in the circulation of patients with acute pancreatitis and certain cancers and in the synovial fluid from patients with rheumatoid arthritis.…”

Section: Introductionmentioning

confidence: 99%

Identification of an autoantigen on the surface of apoptotic human T cells as a new protein interacting with inflammatory group IIA phospholipase A2

Boilard

Bourgoin

Bernatchez

et al. 2003

Blood

100

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One of the most studied secreted phospholipases A 2 (sPLA 2 ), the group IIA sPLA 2 , is found at high levels in inflammatory fluids of patients with autoimmune diseases. A characteristic of group IIA sPLA 2 is its preference for negatively charged phospholipids, which become exposed on the extracellular leaflet of apoptotic cell membranes. We recently showed that low molecular weight heparan sulfate proteoglycans (HSPGs) and uncharacterized detergent-insoluble binding site(s) contribute to the enhanced binding of human group IIA PLA 2 (hGIIA) to apoptotic human T cells. Using matrixassisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry we now identify vimentin as the major HSPG-independent binding protein of hGIIA on apoptotic primary T lymphocytes. Vimentin is partially exposed on the surface of apoptotic T cells and binds hGIIA via its rod domain in a calciumindependent manner. Studies with hGIIA mutants showed that specific motifs in the interfacial binding surface are in- IntroductionPhospholipases A 2 (PLA 2 ) hydrolyze membrane phospholipids to produce free fatty acids and lysophospholipids. 1,2 PLA 2 provide precursors for the biosynthesis of proinflammatory lipid mediators such as prostaglandins, leukotrienes, and lipoxins when the hydrolyzed fatty acid is arachidonic acid (AA) and platelet-activating factor when the lysophospholipid is 1-alkyl-2-lyso-phosphatidylcholine. Several high molecular weight intracellular mammalian PLA 2 and a family of 14-to 19-kDa PLA 2 , referred to as secretory PLA 2 (sPLA 2 ), have been identified. 2,3 Mammalian sPLA 2 are classified into 10 different groups. 3,4 sPLA 2 can interact with external cell membranes through direct binding to phospholipids or specific cell surface receptors. 3,5,6 The M-type receptor present on skeletal muscle 7 and human neutrophils 8 belongs to the superfamily of C-type lectins and binds with high affinity to the snake venom sPLA 2 OS 1 and OS 2 , pancreatic group IB PLA 2 , and rabbit and mouse group IIA PLA 2 but not to bee venom group III PLA 2 and very weakly to human group IIA PLA 2 (hGIIA). 7,[9][10][11][12][13] The N-type receptors identified in rat brain have high affinity for OS 2 and bee venom group III PLA 2 . 14 Venom and mammalian sPLA 2 also bind to a number of cell soluble proteins, such as pentraxins, 15 reticulocalbins, 16 calmodulin, 17 heparin, and to the serum coagulation factor Xa. 18 Several mammalian sPLA 2 such as group II and V enzymes also bind to heparan sulfate proteoglycans (HSPGs) like glypican-1 19 and decorin. 20 hGIIA is found in high concentrations in the circulation of patients with acute pancreatitis and certain cancers and in the synovial fluid from patients with rheumatoid arthritis. 1,2,[21][22][23] hGIIA has been proposed to release AA for the generation of prostaglandins in certain conditions. 19,[24][25][26][27][28][29][30][31] The binding of hGIIA to HSPGs is required for exogenous hGIIA-catalyzed AA release from apoptotic human T cells and from HEK-293 cells overexpressin...

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Inhibition of Prothrombinase by Human Secretory Phospholipase A2 Involves Binding to Factor Xa

Cited by 50 publications

References 52 publications

Remodeling a DNA-binding protein as a specific in vivo inhibitor of bacterial secretin PulD

Remodeling a DNA-binding protein as a specific in vivo inhibitor of bacterial secretin PulD

Cell‐derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a factor VII–dependent mechanism

Identification of an autoantigen on the surface of apoptotic human T cells as a new protein interacting with inflammatory group IIA phospholipase A2

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