Elastase- and plasmin-mediated fibrinolysis in rheumatoid arthritis.
Selected coagulation and fibrinolytic factors were evaluated in plasma and synovial fluid (SF) of 10 rheumatoid arthritis (RA) patients. Increased levels of fibrinogen were observed in plasma (p < 0.01), but only a trace amount of structurally intact fibrinogen was detected in the SF of RA patients, while immunostaining showed deposits of insoluble fibrin in their synovial membranes. Reduced levels of protein C, antithrombin III and coagulation factors II, V, VII, VIII, IX, XII and XIII (p < 0.01), and high levels of thrombin-antithrombin III (TAT) complexes (p < 0.01), were found in SF as compared to their corresponding plasma levels. The increased levels of fibrinogen, TAT complexes, B beta 15-42 peptide and plasminogen activator inhibitor-1 (PAI-1) in plasma (p < 0.01) are consistent with an enhanced fibrin turnover and endothelial perturbation due to a systemic inflammatory state. Plasminogen and alpha 2-plasmin inhibitor activity in SF were significantly reduced as compared to the plasma levels (p < 0.01), whereas an increase in PAI-1 activity was found in SF as compared to plasma (p < 0.01). The detection of D-dimer and B beta 15-42 peptide (p < 0.01) in SF suggests an involvement of plasmin in the degradation of fibrin generated in synovial tissue. The high levels of elastase-alpha 1-proteinase inhibitor complexes and of thrombin-increasable fibrinopeptide A, as well as the pattern of fibrinogen degradation as identified in SF by double-dimension immunoelectrophoresis, suggest that elastase released from exudated granulocytes may play an important role in fibrino(geno)lysis and tissue damage in RA joints.
2nd Medical Clinic, University of Pisa, Italy.
F
F
Carmassi
F
F
De Negri
M
M
Morale
R
R
Puccetti
S I
SI
Chung
D000328:Adult; D000990:Antithrombin III / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000201:enzymology / Q000503:physiopathology; D001779:Blood Coagulation Factors / Q000032:analysis; D005260:Female; D005337:Fibrin / Q000032:analysis; D005341:Fibrinolysin / Q000502:physiology*; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D007122:Immunoelectrophoresis; D007150:Immunohistochemistry; D008297:Male; D010196:Pancreatic Elastase / Q000502:physiology*; D010958:Plasminogen / Q000032:analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011486:Protein C / Q000032:analysis; D013582:Synovial Fluid / Q000737:chemistry; D013583:Synovial Membrane / Q000737:chemistry / Q000196:embryology
D001779:Blood Coagulation Factors; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D000990:Antithrombin III; D005337:Fibrin; D010958:Plasminogen; D010196:Pancreatic Elastase; D005341:Fibrinolysin