Factor Xa as an interface between coagulation and inflammation. Molecular mimicry of factor Xa association with effector cell protease receptor-1 induces acute inflammation in vivo.

Cirino, Giuseppe; Cicala, Carla; Bucci, Mariarosaria; Sorrentino, L.; Ambrosini, Grazia; DeDominicis, G; Altieri, Dario C.

doi:10.1172/jci119428

Cited by 132 publications

(72 citation statements)

References 37 publications

(46 reference statements)

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“…20), we propose that the cellular effectors of endothelial activation by fXa are most likely PAR1 and -2. It is not known whether EPR, a reported fXa receptor in endothelial cells (53), is also involved in this activity. Our results also indicate that thrombin (Fig.…”

Section: Discussionmentioning

confidence: 99%

Synergistic induction of tissue factor by coagulation factor Xa and TNF: Evidence for involvement of negative regulatory signaling cascades

Hezi-Yamit

Wong

Bien-Ly

et al. 2005

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

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Enzymes of the blood coagulation pathway enhance the inflammatory response leading to endothelial dysfunction, accounting, in part, for the vascular complications occurring in sepsis and cardiovascular disease. The responses of endothelial cell activation include induction of the expression of tissue factor (TF), a membrane glycoprotein that promotes thrombosis, and of E-selectin, a cell adhesion molecule that promotes inflammation. In this report, we demonstrate synergistic interactions between the coagulation factor Xa (fXa) and the proinflammatory cytokines TNF, IL-1␤, and CD40L, leading to enhanced expression of TF and E-selectin in endothelial cells. A detailed analysis of the molecular pathways that could account for this activity of fXa showed that fXa inhibited the cytokine-induced expression of dual specificity phosphatases, MAP kinase phosphatase-L, -4, -5, and -7, blocking a negative regulatory effect on c-Jun N-terminal kinase. The synergistic interaction between fXa and TNF was also involved in the inhibition of A20 and I B␣ expression in the I B kinase-NF-B pathway. The data indicate that inhibition of negative regulatory signaling accounts for the amplification of cytokine-induced endothelial cell activation by fXa.cytokines ͉ endothelial cells ͉ factor Xa ͉ inflammation

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Section: Discussionmentioning

confidence: 99%

Synergistic induction of tissue factor by coagulation factor Xa and TNF: Evidence for involvement of negative regulatory signaling cascades

Hezi-Yamit

Wong

Bien-Ly

et al. 2005

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

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“…Platelet-derived microparticles transport arachidonic acid to endothelial cells and induce the expression of cyclooxygenase 2 and the increased production of prostacyclin (43), enhance the interaction between monocytes and endothelial cells (44), and enhance leukocyte aggregation and their accumulation on the endothelium (45). Furthermore, thrombin, factor Xa, and fibrin degradation products are all potent inducers of the inflammatory response (46)(47)(48)(49)(50). Hence, the presence of microparticles in synovial fluid may facilitate not only coagulation, but also inflammation via direct and indirect mechanisms.…”

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

181

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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“…Thrombin is also a potent chemoattractant for macrophages [22], which accumulate in the lungs and BAL fluids of patients with interstitial lung disease [23] and are believed to play an important role in these conditions by producing proinflammatory cytokines and growth factors. More recently, CIRINO et al [24] also provided convincing evidence that factor Xa has potent pro-inflammatory effects in vivo by demonstrating that subplantar injection of factor Xa results in an inflammatory reaction characterized by oedema formation and mast cell infiltration. Although this study was not carried out in the lung, factor Xa may exert similar effects there, and may be particularly important in conditions associated with mast cell recruitment and activation.…”

Section: Role Of Coagulation Cascade Proteins In Pulmonary Inflammatimentioning

confidence: 96%

From clot to collagen: coagulation peptides in interstitial lung disease

Dabbagh¹,

Chambers²,

Guy³

1998

Eur Respir J

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Factor Xa as an interface between coagulation and inflammation. Molecular mimicry of factor Xa association with effector cell protease receptor-1 induces acute inflammation in vivo.

Abstract: Coagulation proteases were tested in a rat model of acute inflammation. Subplantar injection of Factor Xa (10-30 g) produced a time-and dose-dependent edema in the rat paw, and potentiated carrageenin-induced edema. In contrast, the homologous protease Factor IXa was ineffective. This

Cited by 132 publications

References 37 publications

Synergistic induction of tissue factor by coagulation factor Xa and TNF: Evidence for involvement of negative regulatory signaling cascades

Synergistic induction of tissue factor by coagulation factor Xa and TNF: Evidence for involvement of negative regulatory signaling cascades

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

From clot to collagen: coagulation peptides in interstitial lung disease

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