A TRYPSIN SENSITIVE STROMELYSIN ISOLATED FROM RHEUMATOID SYNOVIAL-FLUID IS AN ACTIVATOR FOR MATRIX METALLOPROTEINASES

The processing of synovial fluids of patients suffering from rheumatoi d arthritis led to the characterization of a neutral metalloproteinase with polymorphonuclear leukocyte progelatinase and polymorphonuclear leukocyte procollagenase activating properties. The activator exhibits a relative molecular mass Of M(r)27000 and is an active form of strom elysin. Thus, it reacts specifically with antibodies raised against hu man stromelysin, splits polymorphonuclear leukocyte progelatinase in a manner characteristic of stromelysin, and is inhibited by EDTA as wel l as by a tissue inhibitor of metalloproteinases (TIMP-2). The activat or shows a high specificity for the matrix metalloproteinases, polymor phonuclear leukocyte progelatinase and polymorphonuclear leukocyte pro collagenase. It shows only weak hydrolysis of casein and gelatin, and it does not activate fibroblast M(r)72 000 progelatinase. Brief treatm ent with trypsin does not lead to a significant change in the activato r's relative molecular mass, but induces a rapid loss of its activatin g activity for polymorphonuclear leukocyte progelatinase, while its pr oteolytic activity against the synthetic substrate, )-dinitrophenyl-Pr o-Gln-Gly-Ile-Ala-Gly-Gln-D-Arg, is increased about 3-fold. The same t ryptic treatment does not affect the activator's proteolytic activity towards casein and gelatin.