Collagenases in human synovial fluid.
An enzyme which degrades native collagen at neutral pH has been isolated from cultures of rheumatoid synovium in vitro, but little or no collagenolytic activity has been found in homogenates of fresh rheumatoid synovium. Similar to most other mammalian collagenases this synovial enzyme is readily inhibited by serum proteins. Proteins of synovial fluid are derived largely from serum and synovial fluid from noninflamed joints was found to inhibit synovial collagenase; the inhibitor was destroyed by trypsin, but not by hyaluronidase. Inhibitory activity was reduced in approximately one-half of the fluids from patients with rheumatoid arthritis. In a total of nine synovial fluids, collagenolytic activity was detectable. This activity was not present in constant amounts in synovial fluids aspirated at different times from the same patient and tended to vary inversely with the titer of inhibitory proteins. The collagenolytic activity in the synovial fluids from different patients was variably inhibited by serum proteins. Two distinct collagenases were detected in some rheumatoid synovial fluids and separated by gel filtration. One, labeled "B" enzyme, with an estimated molecular weight 20,000-25,000 resembled the collagenase obtained from synovial cultures. The other, labeled "A" enzyme degraded collagen fibrils as well as collagen in solution. Disc electrophoresis on acrylamide gels and electron microscopy of segment long spacing (SLS) aggregates of reaction products of the enzymes at 27 degrees C demonstrated that both "A" and "B" enzymes cleaved collagen molecules at a point three-quarters from the amino terminal end of the molecule. Thus collagen degradation in rheumatoid arthritis could result from the operation of these two collagenases.
D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D001798:Blood Proteins / Q000494:pharmacology; D002850:Chromatography, Gel; D003094:Collagen / Q000378:metabolism; D004589:Electrophoresis, Disc; D005782:Gels; D006801:Humans; D003012:Microbial Collagenase / Q000032:analysis* / Q000037:antagonists & inhibitors; D008854:Microscopy, Electron; D008970:Molecular Weight; D013582:Synovial Fluid / Q000201:enzymology*
D001798:Blood Proteins; D005782:Gels; D003094:Collagen; D003012:Microbial Collagenase