Identification of tissue inhibitor of metalloproteinase-2 (TIMP-2)-progelatinase complex as the third metalloproteinase inhibitor peak in rheumatoid synovial fluid.
The metalloproteinases are a family of enzymes that can degrade all the components of the extracellular matrix. These potent enzymes are often found in proenzyme forms and require activation before the substrate can be digested. To prevent unlimited connective tissue destruction a number of inhibitors exist to limit their activity. In a previous study it was found that metalloproteinases in proenzyme form and metalloproteinase inhibitors were often present in rheumatoid synovial fluids. Two of these inhibitors were identified in rheumatoid synovial fluid as alpha 2 macroglobulin and tissue inhibitor of metalloproteinase (TIMP), the specific metalloproteinase inhibitor. A third inhibitory peak was unidentified. In the study reported here it was shown that this third inhibitor can be purified using gelatin-Sepharose chromatography and consists of TIMP-2 bound to progelatinase (relative molecular weight 72,000) in a similar way to that found in concentrated connective tissue culture medium. The importance of these proteinase inhibitors in synovial fluid is discussed.
Cawston
T E
TE
Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, UK.
Bigg
H F
HF
Clark
I M
IM
Hazleman
B L
BL
D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D004792:Enzyme Precursors / Q000032:analysis*; D018093:Gelatinases; D006801:Humans; D015151:Immunoblotting; D007719:Knee Joint; D008666:Metalloendopeptidases / Q000032:analysis* / Q000037:antagonists & inhibitors*; D009097:Multienzyme Complexes / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*; D013582:Synovial Fluid / Q000201:enzymology*; D019716:Tissue Inhibitor of Metalloproteinase-2
D004792:Enzyme Precursors; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase