The Primary Plasmin Inhibitor in Rheumatoid Synovial Fluid

Clemmensen, Inge; Donde, René; Andersen, Rune

doi:10.1002/art.1780200709

Cited by 21 publications

(7 citation statements)

References 15 publications

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“…This correlation, combined with the fact that no similarity exists between the levels of PA and plasmin in cartilage, tempts us to speculate that a diffusion of plasmin from the synovium to the cartilage could be an important contributing factor in the enzymatic cascade responsible for the degradation of the extracellular matrix. In addition, a certain amount of local plasmin synthesis in the synovial fluid is possible, since significant levels of plasminogen and PA have been found in inflammatory fluid from patients with rheumatoid arthritis (17,42).…”

Section: Discussionmentioning

confidence: 99%

Imbalance between the mechanisms of activation and inhibition of metalloproteases in the early lesions of experimental osteoarthritis

Pelletier

Mineau

Faure

et al. 1990

Arthritis & Rheumatism

124

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Levels of tissue inhibitor of metalloproteases (TIMP) and plasminogen activator (PA)/plasmin were measured and the distribution of PA was studied by immunohistochemical techniques in cartilage and synovium samples from dogs subjected to sectioning of the anterior cruciate ligament of their right knees and sham operation of their left knees (controls). Twenty-three animals were divided into 3 groups and killed at 2,4, or 8 weeks after surgery. The levels of PA and plasmin were found to be significantly elevated in the osteoarthritic (OA) knee cartilage and synovium at all times after surgery, except for levels of PA in the OA cartilage at 2 weeks. There was a positive correlation between the levels of PA and plasmin in the synovial membrane (r = 0.64, P < 0.001). In OA knees, the presence of high levels of total and active collagenase was detected in cartilage and in synovium. The levels of these 2 forms of collagenase showed a positive correlation both in cartilage (r = 0.65, P < 0.001) and in synovium (r = 0.77, P < 0.001). The levels of TIMP in cartilage from OA and sham operated knees were similar. Although the TIMP level was increased in the OA synovium, it was found 30, 1990. only in trace amounts in cartilage. Immunohistochemical studies revealed that both forms of PA, urokinasetype PA and tissue-type PA, and TIMP were present in OA tissues. In the synovium, they were found mainly in monocyte/macrophages, synovial lining cells, and blood vessel cells. In OA cartilage, PA was present only at the superficial level in chondrocytes and in cartilage matrix, whereas TIMP was present in chondrocyte lacunae throughout the full thickness of the cartilage. TIMP was also detected in the superficial level of cartilage from sham operated knees. The results of this study indicate that in OA tissues, there are conditions that favor the synthesis and activation of metalloproteases. PA and plasmin are likely to play an important role in the physiologic activation of metalloproteases, although they are probably not the only system involved in this process. The lack of increased TIMP levels in the OA cartilage, in the presence of increased metalloprotease activity, is also a possible contributing factor in the enzymatic degradation of this tissue.Osteoarthritis (OA) is a multifactorial disease in which several complex mechanisms lead to a progressive destruction of joints. The frequent involvement of diarthrodial, weight-bearing joints is largely responsible for the morbidity of OA. The primary changes seem to appear in the articular cartilage and involve both extrinsic and intrinsic factors. Among the latter, anatomic or mechanical disturbances may be of major importance in the development of OA (1). According to the mechanical factors involved in this disease, researchers have developed several experimental animal models of OA (2). One of the difficulties with many of these models is that the lesions created are often rapidly progressive and very severe.

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Section: Discussionmentioning

confidence: 99%

Imbalance between the mechanisms of activation and inhibition of metalloproteases in the early lesions of experimental osteoarthritis

Pelletier

Mineau

Faure

et al. 1990

Arthritis & Rheumatism

124

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“…Rheumatoid patients, on the other hand, have difficulties in the removal of fibrin clots. [9][10][11] This imbalance is not dependent on the existence of an inefficacious plasminogen system in rheumatoid hosts, and in fact fibrinolysis seems reasonably activated in their joints. 12 Several factors can account for the difficult dissolution of fibrin clots.…”

Section: Coagulation Inside the Joint Spacementioning

confidence: 99%

A fibrin based model for rheumatoid synovitis

Sánchez‐Pernaute

Largo²,

Calvo³

et al. 2003

Annals of the Rheumatic Diseases

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“…Clemmensen and Andersen (1 978) consider that fibrin degradation-products from inflamed tissues are important components of the " fibrin " at such sites and that these are relatively resistant to further breakdown. Other mechanisms may be the presence of fibrinolytic inhibitors (Van der Putte, Hegt and Overbeek, 1977) or that the fibrin in joints is a poor substrate for plasmin (Clemmensen, Donde and Andersen, 1977). The situation can be inferred to be similar in antigen-induced arthritis.…”

Section: Discussionmentioning

confidence: 99%

The role of Fibronectin in the pathogenesis of antigen‐induced arthritis in the rabbit

Scott¹,

Almond²,

Walton³

et al. 1983

The Journal of Pathology

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Fibronectin (FN), a high molecular weight glycoprotein, is present in plasma and is a normal structural component of the synovium in the rabbit, as it is in man. FN is also involved in the sequence of changes seen in synovium in experimental antigen-induced arthritis. Its widespread distribution in inflamed synovia in the initial acute phase of induced arthritis probably merely reflects the presence of FN of plasma origin in serous exudates. In established experimental arthritis, FN co-distributes with fibrin, while in synovia undergoing organisation, FN is present intracellularly in several types of mesenchymal cells (suggesting local synthesis) and is deposited on immature collagen fibrils. However, it is no longer present when mature collagen is formed. The persistence of FN, along with fibrin, in inflamed joints, and its involvement in fibrosis, suggest that it may play a significant part in determining the chronicity of this form of experimental arthritis.

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The Primary Plasmin Inhibitor in Rheumatoid Synovial Fluid

Cited by 21 publications

References 15 publications

Imbalance between the mechanisms of activation and inhibition of metalloproteases in the early lesions of experimental osteoarthritis

Imbalance between the mechanisms of activation and inhibition of metalloproteases in the early lesions of experimental osteoarthritis

A fibrin based model for rheumatoid synovitis

The role of Fibronectin in the pathogenesis of antigen‐induced arthritis in the rabbit

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