Fibrin promotion and lysis in arthritic joints.

Barnhart, Marion I.; Riddle, Jeanne M.; Bluhm, Gilbert B.; Quintana, Clotilde

doi:10.1136/ard.26.3.206

Cited by 54 publications

(27 citation statements)

References 19 publications

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“…It was demonstrated that fibrinogen and fibrin contribute to inflammation by inducing leukocyte migration (22)(23)(24). Later, in vitro and in vivo studies demonstrated that fibrin(ogen) alters inflammation not only by affecting leukocyte migration, but also by directly modulating the inflammatory response of leukocytes and ECs via an increased cytokine/chemokine response.…”

Section: Inflammatory Potential Of Fibrinogen and Fibrinmentioning

confidence: 99%

Novel Aspects of Fibrin(ogen) Fragments during Inflammation

Jennewein

Tran

Paulus

et al. 2011

Mol Med

208

139

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Coagulation is fundamental for the confinement of infection and/or the inflammatory response to a limited area. Under pathological inflammatory conditions such as arthritis, multiple sclerosis or sepsis, an uncontrolled activation of the coagulation system contributes to inflammation, microvascular failure and organ dysfunction. Coagulation is initiated by the activation of thrombin, which, in turn, triggers fibrin formation by the release of fibrinopeptides. Fibrin is cleaved by plasmin, resulting in clot lysis and an accompanied generation of fibrin fragments such as D and E fragments. Various coagulation factors, including fibrinogen and/or fibrin [fibrin(ogen)] and also fibrin degradation products, modulate the inflammatory response by affecting leukocyte migration and cytokine production. Fibrin fragments are mostly proinflammatory, however, Bβ15-42 in particular possesses potential antiinflammatory effects. Bβ15-42 inhibits Rho-kinase activation by dissociating Fyn from Rho and, hence prevents stress-induced loss of endothelial barrier function and also leukocyte migration. This article summarizes the state-of-the-art in inflammatory modulation by fibrin(ogen) and fibrin fragments. However, further research is required to gain better understanding of the entire role fibrin fragments play during inflammation and, possibly, disease development.

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Section: Inflammatory Potential Of Fibrinogen and Fibrinmentioning

confidence: 99%

Novel Aspects of Fibrin(ogen) Fragments during Inflammation

Jennewein

Tran

Paulus

et al. 2011

Mol Med

208

139

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“…Fibrin deposition, the culmination of the coagulation cascade, is a hallmark of RA synovium (2,3). Deposited fibrin can promote inflammatory responses (4), while citrulline-modified fibrin(ogen) is a prominent target of RA-specific autoantibodies (5).…”

Section: Introductionmentioning

confidence: 99%

Plasma carboxypeptidase B downregulates inflammatory responses in autoimmune arthritis

Song¹,

Hwang²,

Cho³

et al. 2011

J. Clin. Invest.

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The immune and coagulation systems are both implicated in the pathogenesis of rheumatoid arthritis (RA). Plasma carboxypeptidase B (CPB), which is activated by the thrombin/thrombomodulin complex, plays a procoagulant role during fibrin clot formation. However, an antiinflammatory role for CPB is suggested by the recent observation that CPB can cleave proinflammatory mediators, such as C5a, bradykinin, and osteopontin. Here, we show that CPB plays a central role in downregulating C5a-mediated inflammatory responses in autoimmune arthritis. CPB deficiency exacerbated inflammatory arthritis in a mouse model of RA, and cleavage of C5a by CPB suppressed the ability of C5a to recruit immune cells in vivo. In human patients with RA, genotyping of nonsynonymous SNPs in the CPB-encoding gene revealed that the allele encoding a CPB variant with longer half-life was associated with a lower risk of developing radiographically severe RA. Functionally, this CPB variant was more effective at abrogating the proinflammatory properties of C5a. Additionally, expression of both CPB and C5a in synovial fluid was higher in patients with RA than in those with osteoarthritis. These findings suggest that CPB plays a critical role in dampening local, C5a-mediated inflammation and represents a molecular link between inflammation and coagulation in autoimmune arthritis.

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“…Both Cl and C3 also may be activated directly by plasmin (28). A relationship of this activity to our observations is a distinct possibility as both fibrinogen and evidence of fibrinolysis have been observed within joint fluids in other rheumatic diseases (29). These factors were not examined in the present study.…”

Section: Methodsmentioning

confidence: 53%